EP-4734964-A1 - LIPID PARTICLES FOR DELIVERING A PAYLOAD

Abstract

Provided herein are lipid particles, pharmaceutical compositions comprising the lipid particles described herein, and methods of use comprising administering the lipid particles described herein.

Inventors

• JHAVERI, Aditi M.
• WESTCOTT, Nathan
• PAJEROWSKI, John David

Assignees

• Repertoire Immune Medicines, Inc.

Dates

Publication Date

20260506

Application Date

20240628

Claims (1)

1. WHAT IS CLAIMED IS: 1. A lipid particle comprising cholesteryl hemisuccinate (“CHEMS”) and a payload and optionally one or more of: a. one or more ionizable lipids; b. one or more neutral lipids; c. one or more sterols; and d. one or more stealth lipids. 2. A method of targeting a payload to a spleen of a subject in vivo comprising combining a lipid particle or a composition comprising the payload encapsulated within a lipid particle or a composition comprising CHEMS in a molar amount of at least 11%. 3. The method of claim 2, wherein the lipid particle or composition further comprises one or more ionizable lipids, one or more neutral lipids, one or more sterols, one or more stealth lipids, or any combination thereof. 4. The lipid particle of claim 1 or the method of claim 2 or 3, wherein the lipid particle delivers the payload to the spleen. 5. The lipid particle of claim 1 or 4 or the method of claim 2 or 3, wherein the ratio of the payload delivered to the spleen versus liver is greater than 1.1. 6. The lipid particle of any one of claims 1, 4, and 5 or the method of any one of claims 2-5, wherein the ratio of the payload delivered to the spleen versus liver is about 1.1 to about 12. 7. The lipid particle of any one of claims 1 and 4-6 or the method of any one of claims 2-6, wherein the ratio of payload delivered to the spleen versus liver is about 4 to about 11. 8. The lipid particle of any one of claims 1 and 4-7 or the method of any one of claims 2-7, wherein the ratio of payload delivered to the spleen versus liver is determined using an imaging system. 9. The lipid particle of a claim 8 or the method of claim 8, wherein the imaging system is a LICOR Pearl Trilogy imaging system using Image Studio software from LICOR version 5.2.5. 10. The lipid particle of any one of claims 1 and 4-9 or the method of any one of claims 2-9, wherein the CHEMS in the lipid particle is in a molar amount of at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, or at least 20%. 11. The lipid particle of any one of claims 1 and 4-10 or the method of any one of claims 2- 10, wherein the CHEMS in the lipid particle is in a molar amount of about 11% to about 45%, about 15% to about 45%, about 20% to about 45%, about 5% to about 40% about 7.5% to about 40%, about 10% to about 40%, about 15% to about 40%, about 20% to about 40%, about 5% to about 35%, about 7.5% to about 35%, about 10% to about 35%, about 15% to about 35%, about 20% to about 35%, about 5% to about 30%, about 7.5% to about 30%, about 10% to about 30%, about 15% to about 30%, about 20% to about 30%, about 5% to about 25%, about 7.5% to about 25%, about 10% to about 25%, about 15% to about 25%, or about 20% to about 25%. 12. The lipid particle of any one of claims 1 and 4-11 or the method of any one of claims 2- 11 wherein the CHEMS in the lipid particle is in a molar amount of about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, about 20%, about 25%, about 30%, about 35%, about 40%, or about 45%. 13. The lipid particle of any one of claims 1 and 4-11 or the method of any one of claims 2- 11, wherein the CHEMS in the lipid particle is in a molar amount of about 11% to about 20%, about 20% to about 30%, or about 11% to about 30%. 14. The lipid particle of any one of claims 1 and 4-11 or the method of any one of claims 2- 11, wherein the CHEMS in the lipid particle is in a molar amount of about 11% to about 20%. 15. The lipid particle of any one of claims 1 and 4-11 or the method of any one of claims 2- 11, wherein the CHEMS in the lipid particle is in a molar amount of about 11%. 16. The lipid particle of any one of claims 1 and 4-11 or the method of any one of claims 2- 11, wherein the CHEMS in the lipid particle is in a molar amount of about 15%. 17. The lipid particle of any one of claims 1 and 4-11 or the method of any one of claims 2- 11, wherein the CHEMS in the lipid particle is in a molar amount of about 20%. 18. The lipid particle of any one of claims 1 and 4-11 or the method of any one of claims 2- 11, wherein the CHEMS in the lipid particle is in a molar amount of about 25%. 19. The lipid particle of any one of claims 1 and 4-18 or the method of any one of claims 2- 18, wherein the lipid particle comprises one or more ionizable lipids. 20. The lipid particle of any one of claims 1 and 4-19 or the method of any one of claims 2- 19, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, or at least 20%. 21. The lipid particle of any one of claims 1 and 4-20 or the method of any one of claims 2- 20, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 20% to about 70%. 22. The lipid particle of any one of claims 1 and 4-21 or the method of any one of claims 2- 21, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 25% to about 65%, about 30% to about 65%, about 35% to about 65%, about 45% to about 65%, about 50% to about 65%, about 25% to about 60%, about 30% to about 60%, about 35% to about 60%, about 45% to about 60%, about 50% to about 60%, about 25% to about 55%, about 30% to about 55%, about 35% to about 55%, about 45% to about 55%, about 50% to about 55%, about 25% to about 50%, about 30% to about 50%, about 35% to about 50%, or about 45% to about 50%. 23. The lipid particle of any one of claims 1 and 4-21 or the method of any one of claims 2- 21, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, or about 65%. 24. The lipid particle of any one of claims 1 and 4-21 or the method of any one of claims 2- 21, wherein the one or more ionizable lipids in the lipid particle are in a molar in a molar amount of about 30% to about 60%. 25. The lipid particle of any one of claims 1 and 4-21 or the method of any one of claims 2- 21, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 40% to about 60%. 26. The lipid particle of any one of claims 1 and 4-21 or the method of any one of claims 2- 21, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 40% to about 50%. 27. The lipid particle of any one of claims 1 and 4-21 or the method of any one of claims 2- 21, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 50% to about 60%. 28. The lipid particle of any one of claims 1 and 4-21 or the method of any one of claims 2- 21, wherein the one or more ionizable lipids in the lipid particle is present in a molar amount of about 30%. 29. The lipid particle of any one of claims 1 and 4-21 or the method of any one of claims 2- 21, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 40%. 30. The lipid particle of any one of claims 1 and 4-21 or the method of any one of claims 2- 21, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 50%. 31. The lipid particle of any one of claims 1 and 4-21 or the method of any one of claims 2- 21, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 55%. 32. The lipid particle of any one of claims 1 and 4-21 or the method of any one of claims 2- 21, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 60%. 33. The lipid particle of any one of claims 1 and 4-21 or the method of any one of claims 2- 21, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 65%. 34. The lipid particle of any one of claims 1 and 4-21 or the method of any one of claims 2- 21, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 70%. 35. The lipid particle of any one of claims 1 and 4-34 or the method of any one of claims 2- 34, wherein the one or more ionizable lipids in the lipid particles are one or more selected from the group consisting of DLin-MC3-DMA (“MC3”), DLin-KC2-DMA (“KC2”), ssPalmO-Phe (“SS-OP”), C12-200, SM-102, α-D-tocopherolsuccinoyl (“SS-EC”), ALC-0315 (“ALC”), Tri-N- tridecyl 3-(ethyl(methyl)amino)propanoate (“304-O13”), tetrakis(2-(octyldisulfaneyl)ethyl) 3,3',3'',3'''-(((methylazanediyl)bis(propane-3,1-diyl))bis(azanetriyl))tetrapropionate (“306- O12B”), 9-[4-(dimethylamino)-1-oxobutoxy]-heptadecanedioic acid, 1,17-di-(2Z)-2-nonen-1-yl ester (“L319”), 9,12-octadecadienoic acid, (9Z,12Z)-1,1′,1′′,1′′′-[(3,6-dioxo-2,5- piperazinediyl)bis(4,1-butanediylnitrilodi-4,1-butanediyl)] ester (“OF-C4-Deg-Lin”), 2- (dioctylamino)ethyl nonyl hydrogen phosphate (“9A1P9”), 5-(((3- (dibutylamino)propyl)amino)methyl)-6-hydroxyundecane-1,11-diyl (9Z,9'Z,12Z,12'Z)- bis(octadeca-9,12-dienoate) (“IR-117-17”), 9Z,12Z-octadecadienoic acid, 3-[4,4-bis(octyloxy)-1- oxobutoxy]-2-[[[[3-(diethylamino)propoxy]carbonyl]oxy]methyl]propyl ester (“LP-01”) and 4A3-SC8. 36. The lipid particle of any one of claims 1 and 4-35 or the method of any one of claims 2- 35, wherein the one or more ionizable lipids in the lipid particle are one or more selected from the group consisting of DLin-MC3-DMA (“MC3”), DLin-KC2-DMA (“KC2”), ssPalmO-Phe ("SS-OP"), C12-200, SM-102, α-D-tocopherolsuccinoyl (“SS-EC”), and ALC-0315 (“ALC”). 37. The lipid particle of claim 36 or the method of claim 36, wherein the one or more ionizable lipids in the lipid particle are one or more selected from the group consisting of ssPalmO-Phe ("SS-OP"), C12-200, SM-102, and ALC-0315 (“ALC”). 38. The lipid particle of any one of claims 1 and 4-37 or the method of any one of claims 2- 36, wherein only one ionizable lipid is in the lipid particle. 39. The lipid particle of claim 37 or the method of claim 38, wherein the only ionizable lipid in the lipid particle is SS-OP. 40. The lipid particle of claim 39 or the method of claim 39, wherein when administered to a subject in need thereof, the subject exhibits one or more of: (i) an increase in Treg cells, (ii) reduction in effector T cells, (iii) reduction in B-cells, (iv) reduction in cytokine production, (v) reduction in activated B cells; (vi) reduction in activated effector T cells; or (vii) any combination thereof. 41. The lipid particle of claim 39 or 40 or the method of claim 39 or 40, which when administered to a subject in need thereof, reduces B-cell levels in the subject. 42. The lipid particle of claim 39 or 40 or the method of claim 39 or 40, which when administered to a subject in need thereof, reduces B-cell levels in the subject as compared with a reference lipid particle containing an ionizable lipid other than SS-OP. 43. The lipid particle of claim 39 or 40 or the method of claim 39 or 40, which when administered to a subject in need thereof, reduces B-cell levels in the subject as compared with a reference lipid particle containing MC-3 as the ionizable lipid. 44. The lipid particle of any one of claims 39-43 or the method of any one of claims 39-43, which when administered to a subject in need thereof, reduces T-cell levels in the subject. 45. The lipid particle of any one of claims 39-43 or the method of any one of claims 39-43, which when administered to a subject in need thereof, reduces T-cell levels in the subject as compared with a reference lipid particle containing an ionizable lipid other than SS-OP. 46. The lipid particle of any one of claims 39-43 or the method of any one of claims 39-43, which when administered to a subject in need thereof, reduces T-cell levels in the subject as compared with a reference lipid particle containing MC-3 as the ionizable lipid. 47. The lipid particle of any one of claims 39-46 or the method of any one of claims 39-46, which when administered to a subject in need thereof, reduces levels of IFN-α in the subject. 48. The lipid particle of any one of claims 39-46 or the method of any one of claims 39-46, which when administered to a subject in need thereof, reduces levels of IFN-α in the subject as compared with a reference lipid particle containing an ionizable lipid other than SS-OP 49. The lipid particle of any one of claims 39-46 or the method of any one of claims 39-46, which when administered to a subject in need thereof, reduces levels of IFN-α in the subject as compared with a reference lipid particle containing MC-3 as the ionizable lipid. 50. The lipid particle of any one of claims 1 and 4-49 or the method of any one of claims 2- 49, wherein the one or more ionizable lipids in the lipid particle comprises α-D- tocopherolsuccinoyl (“SS-EC”). 51. The lipid particle of claim 50 or the method of claim 50, which when administered to a subject in need thereof, increases B-cell levels in the subject. 52. The lipid particle of claim 50 or the method of claim 50, which when administered to a subject in need thereof, increases B-cell levels in the subject as compared with a reference lipid particle containing an ionizable lipid other than SS-EC. 53. The lipid particle of claim 50 or the method of claim 50, which when administered to a subject in need thereof, increases B-cell levels in the subject as compared with a reference lipid particle containing MC-3 as the ionizable lipid. 54. The lipid particle of any one of claims 50-53 or the method of any one of claims 50-53, which when administered to a subject in need thereof, increases T-cell levels in the subject. 55. The lipid particle of any one of claims 50-53 or the method of any one of claims 50-53, which when administered to a subject in need thereof, increases T-cell levels in the subject as compared with a reference lipid particle containing an ionizable lipid other than SS-EC. 56. The lipid particle of any one of claims 50-53 or the method of any one of claims 50-53, which when administered to a subject in need thereof, increases T-cell levels in the subject as compared with a reference lipid particle containing MC-3 as the ionizable lipid. 57. The lipid particle of any one of claims 50-53 or the method of any one of claims 50-53, which when administered to a subject in need thereof, increases levels of IFN-α in the subject. 58. The lipid particle of any one of claims 50-53 or the method of any one of claims 50-53, which when administered to a subject in need thereof, increases levels of IFN-α in the subject as compared with a reference lipid particle containing an ionizable lipid other than SS-EC. 59. The lipid particle of any one of claims 50-53 or the method of any one of claims 49-52, which when administered to a subject in need thereof, increases levels of IFN-α in the subject as compared with a reference lipid particle containing MC-3 as the ionizable lipid. 60. The lipid particle of any one of claims 1 and 4-59 or the method of any one of claims 2- 59, wherein the lipid particle comprises one or more neutral lipids 61. The lipid particle of claim 60 or the method of claim 60, wherein the one or more neutral lipids in the lipid particle are in a molar amount of at least 0.5%, at least 0.6%, at least 0.7%, at least 0.8%, at least 0.9%, at least 1.1%, at least 1.2%, at least 1.3%, at least 1.4%, at least 1.5%, at least 1.6%, at least 1.7%, at least 1.8%, at least 1.9%, at least 2%, at least 2.1%, at least 2.2%, at least 2.3%, at least 2.4%, or at least 2.5%. 62. The lipid particle of claim 60 or the method of claim 60, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 2.5% to about 25%, about 2.5% to about 20%, about 2.5% to about 17.5%, about 2.5% to about 15%, about 2.5% to about 12.5%, about 2.5% to about 10%, about 5% to about 25%, about 5% to about 20%, about 5% to about 17.5%, about 5% to about 15%, about 5% to about 12.5%, about 5% to about 10%, about 7.5% to about 25%, about 7.5% to about 20%, about 7.5% to about 17.5%, about 7.5% to about 15%, about 7.5% to about 12.5%, about 7.5% to about 10%, about 10% to about 25%, about 10% to about 20%, about 10% to about 17.5%, about 10% to about 15%, about 10% to about 12.5%, about 12.5% to about 25%, about 12.5% to about 20%, about 12.5% to about 17.5%, or about 12.5% to about 15%. 63. The lipid particle of claim 60 or the method of claim 60, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 5%, about 7.5%, about 10%, about 12.5%, about 15%, about 17.5%, about 20%, about 22.5%, or about 25%. 64. The lipid particle of claim 60 or the method of claim 60, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 5% to about 20%. 65. The lipid particle of claim 60 or the method of claim 60, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 7.5% to about 17.5%. 66. The lipid particle of claim 60 or the method of claim 60, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 2.5%. 67. The lipid particle of claim 60 or the method of claim 60, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 5%. 68. The lipid particle of claim 60 or the method of claim 60, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 7.5%. 69. The lipid particle of claim 60 or the method of claim 60, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 10%. 70. The lipid particle of claim 60 or the method of claim 60, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 12.5%. 71. The lipid particle of claim 60 or the method of claim 60, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 15%. 72. The lipid particle of claim 60 or the method of claim 60, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 17.5%. 73. The lipid particle of claim 60 or the method of claim 60, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 20%. 74. The lipid particle of claim 60 or the method of claim 60, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 25%. 75. The lipid particle of any one of claims 60-74 or the method of any one of claims 60-74, wherein the one or more neutral lipids in the lipid particles are one or more phosphatidylcholine (“PC”), phosphatidylethanolamine (“PE”), and combination thereof. 76. The lipid particle of any one of claims 60-74 or the method of any one of claims 60-74, wherein the one or more neutral lipids in the lipid particle are one or more selected from the group consisting of 1,2-diastearoyl-sn-glycero-3-phosphocholine ("DSPC"), 1,2-dioleoyl-sn- glycero-3-phosphocholine (“DOPC”), 1,2- dioctadecanoyl-sn-glycerol (“DSDG”), 1-2-dioleoyl- sn-glycerol, 1-2-di-(9Z-octadecenoyl)-sn-glycerol ("DODG"), 1,2-dioleoyl-sn-glycero-3- phosphoethanolamine ("DOPE"), diacylphosphatidylcholine, diacylphosphatidylethanolamine, ceramide, sphingomyelin, cephalin, cerebrosides, diacylglycerols dipalmitoylphosphatidylcholine (“DPPC”), palmitoyloleoyl-phosphatidylcholine (“POPC”), palmitoyloleoyl- phosphatidylethanolamine (“POPE”), palmitoyloleyol-phosphatidylglycerol (POPG), dipalmitoyl-phosphatidylethanolamine (“DPPE”), dimyristoyl-phosphatidylethanolamine (“DMPE”), distearoyl-phosphatidylethanolamine (“DSPE”), monomethyl- phosphatidylethanolamine, dimethyl-phosphatidylethanolamine, dielaidoyl- phosphatidylethanolamine (“DEPE”), stearoyloleoyl-phosphatidylethanolamine (“SOPE”), and egg phosphatidylcholine (“EPC”). 77. The lipid particle of claim 76 or the method of claim 76, wherein the one or more neutral lipids in the lipid particle are DOPE, DODG, or a combination thereof. 78. The lipid particle of claim 76 or 77 or the method of claim 76 or 77, wherein only one neutral lipid is in the lipid particle. 79. The lipid particle of claim 78 or the method of claim 78, wherein the only neutral lipid in the lipid particle is DOPE. 80. The lipid particle of claim 78 or the method of claim 78, wherein the only neutral lipid in the lipid particle is DODG. 81. The lipid particle of any one of claims 1 and 4-80 or the method of any one of claims 2- 80, wherein the lipid particle comprises one or more sterols. 82. The lipid particle of claim 81 or the method of claim 81, wherein the one or more sterols in the lipid particle are in a molar amount of at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, at least 10%, at least 11%, at least 12%, at least 13%, at least 14%, at least 15%, at least 16%, at least 17%, at least 18%, at least 19%, or at least 20%. 83. The lipid particle of claim 81 or the method of claim 81, wherein the one or more sterols in the lipid particle are in a molar amount of about 20% to about 50%, about 20% to about 45%, about 25% to about 45%, about 30% to about 45%, about 35% to about 45%, about 40% to about 45%, about 20% to about 40%, about 25% to about 40%, about 30% to about 40%, about 35% to about 40%, about 20% to about 30%, about 25% to about 30%, or about 20% to about 25%. 84. The lipid particle of claim 81 or the method of claim 81, wherein the one or more sterols in the lipid particle are in a molar amount of about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 50%. 85. The lipid particle of claim 81 or the method of claim 81, wherein the one or more sterols in the lipid particle are in a molar amount of about 20% to about 40%. 86. The lipid particle of claim 81 or the method of claim 81, wherein the one or more sterols in the lipid particle are in a molar amount of about 20% to about 30%. 87. The lipid particle of claim 81 or the method of claim 81, wherein the one or more sterols in the lipid particle are in a molar amount of about 30% to about 40%. 88. The lipid particle of claim 81 or the method of claim 81, wherein the one or more sterols in the lipid particle are in a molar amount of about 20%. 89. The lipid particle of claim 81 or the method of claim 81, wherein the one or more sterols in the lipid particle are in a molar amount of about 28.5%. 90. The lipid particle of claim 81 or the method of claim 81, wherein the one or more sterols in the lipid particle are in a molar amount of about 30%. 91. The lipid particle of claim 81 or the method of claim 81, wherein the one or more sterols in the lipid particle are in a molar amount of about 38.5%. 92. The lipid particle of claim 81 or the method of claim 81, wherein the one or more sterols in the lipid particle are in a molar amount of about 40%. 93. The lipid particle of any one of claims 81-92 or the method of any one of claims 81-92, wherein the one or more sterols in the lipid particle are cholesterol, β-sitosterol, stigmasterol, campesterol, fucosterol, brassicasterol, ergosterol, 9,11-dehydroergosterol, daucosterol, β- sitosterol acetate, or other C-24 alkyl derivatives, and combinations thereof 94. The lipid particle of any one of claims 81-92 or the method of any one of claims 81-92, wherein the one or more sterols in the lipid particle are cholesterol, β-sitosterol, and combinations thereof. 95. The lipid particle of any one of claims 81-93 or the method of any one of claims 81-94, wherein only one sterol is in the lipid particle. 96. The lipid particle of claim 95 or the method of claim 95, wherein the only sterol in the lipid particle is cholesterol. 97. The lipid particle of any one of claims 1 and 4-96 or the method of any one of claims 2- 96, wherein the lipid particle comprises one or more stealth lipids. 98. The lipid particle of claim 97 or the method of claim 97, wherein the one or more stealth lipids in the lipid particle are in a molar amount of at least 0.1%, at least 0.15%, at least 0.2%, or at least 0.25%. 99. The lipid particle of claim 97 or the method of claim 97, wherein the one or more stealth lipids in the lipid particle are in a molar amount of about 0.25% to about 3%, about 0.5% to about 3%, about 1% to about 3%, about 1.5% to about 3%, about 2% to about 3%, about 2.5% to about 3%, about 0.25% to about 2.5%, about 0.5% to about 2.5%, about 1% to about 2.5%, about 1.5% to about 2.5%, about 2% to about 2.5%, about 0.25% to about 2%, about 0.5% to about 2%, about 1% to about 2%, about 1.5% to about 2%, about 0.25% to about 1.5%, about 0.5% to about 1.5%, or about 1% to about 1.5%. 100. The lipid particle of claim 97 or the method of claim 97, wherein the one or more stealth lipids in the lipid particle are in a molar amount of about 1% to about 3%. 101. The lipid particle of claim 97 or the method of claim 97, wherein the one or more stealth lipids in the lipid particle are in a molar amount of about 0.5%, about 1%, about 1.5%, about 2%, about 2.5%, or about 3%. 102. The lipid particle of claim 97 or the method of claim 97, wherein the one or more stealth lipids in the lipid particle are in a molar amount of about 1%. 103. The lipid particle of claim 974 or the method of claim 97, wherein the one or more stealth lipids in the lipid particle are in a molar amount of about 1.5%. 104. The lipid particle of claim 97 or the method of claim 97, wherein the one or more stealth lipids in the lipid particle are in a molar amount of about 2%. 105. The lipid particle of claim 97 or the method of claim 97, wherein the one or more stealth lipids in the lipid particle are in a molar amount of about 2.5%. 106. The lipid particle of claim 97 or the method of claim 97, wherein the one or more stealth lipids in the lipid particle are in a molar amount of about 3%. 107. The lipid particle of any one of claims 97-106 or the method of any one of claims 94-103, wherein the one or more stealth lipids are one or more PEG terminated lipids, one or more polysarcosine derivatives, or combinations thereof. 108. The lipid particle of claim 107 or the method of claim 107, wherein the one or more stealth lipids are one or more PEG terminated lipids. 109. The lipid particle of claim 108 or the method of claim 108, wherein the one or more PEG terminated lipids in the lipid particle are one or more selected from the group consisting of 1,2- dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 ("DMG-PEG2000"), distearoyl-rac- glycerol-PEG2K (“DSG-PEG2k”), [(2R)-2,3-di(octadecanoyloxy)propyl] 2-(2- methoxyethoxycarbonylamino)ethyl phosphate ("C18-mPEG2000"), [3-[3-(2- methoxyethoxy)propylcarbamoyloxy]-2-tetradecanoyloxypropyl] tetradecanoate (“PEG2000-c- DMG”), 3-[hydroxy-[2-[2-(2-methoxyethoxy)ethylamino]ethoxy]phosphoryl]oxy-2- tetradecanoyloxypropyl] tetradecanoate ("DMPE-PEG2000"), 1,2-distearoyl-sn-glycero-3- phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] ("18:1 PEG2000-PE"), 1,2- distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] ("DSPE- PEG2000-COOH), and Bis(1,2-distearoyl-sn-glycero-3-phosphoethanolamine)-N-[(polyethylene glycol)-2000] ("Bis-DSPE-PEG2000"). 110. The lipid particle of claim 109 or the method of claim 109, wherein the one or more PEG terminated lipids in the lipid particle is DMG-PEG2000, DMPE-PEG2000, or a combination thereof. 111. The lipid particle of any one of claims 108-110 or the method of any one of claims 105- 107, wherein only one PEG terminated lipid is in the lipid particle. 112. The lipid particle of claim 108 or the method of claim 111, wherein the only PEG terminated lipid in the lipid particle is DMG-PEG2000. 113. The lipid particle of claim 108 or the method of claim 111, wherein the only PEG terminated lipid in the lipid particle is DMPE-PEG2000. 114. The lipid particle of claim 108 or the method of claim 111, wherein the only PEG terminated lipid in the lipid particle is PEG2000-PE. 115. The lipid particle of claim 104 or the method of claim 107, wherein the one or more stealth lipids are one or more polysarcosine derivative. 116. The lipid particle of claim 112 or the method of claim 115, wherein the one or more polysarcosine derivatives in the lipid particle are one or more selected from the group consisting of N-tetradecyl-polysarcosine-25 (“N-tetradecyl-pSar25”), N-hexadecyl-polysarcosine-25 (“N- hexadecyl-pSar25”), N-octadecyl-polysarcosine-25, N-dodecyl-polysarcosine-25 (“N-octadecyl- pSar25”), 1,2-dimyristoyl-sn-glycero-3-succinyl-N-polysarcosine-25 (“DMG-pSar25”), 1,2- dioleoyl-sn-glycero-3-phosphoethanolamine-N-polysarcosine-25 (ammonium salt) (“18:1 PE (DOPE), N,N-ditetradecylamine-N-succinyl[methyl(polysarcosine)45] (“N-TETAMINE- pSar45”), N,N-ditetradecylamine-N-succinyl[methyl(polysarcosine)35] (“N-TETAMINE- pSar35”), N,N-ditetradecyl-polysarcosine-25 (“N-TETAMINE-pSar25”), N-TETAMINE- pSar45-maleimide, or N-TETAMINE-PEOZ-40. 117. The lipid particle of claim 115 or 116 or the method of claim 115 or 116, wherein only one polysarcosine derivative is in the lipid particle. 118. The lipid particle of claim 1 or the method of claim 2 or 3, wherein the lipid particle comprises about 25% to about 45% of SS-OP, about 5% to about 25% of DODG, about 15% to about 35% of cholesterol, about 11% to about 30% CHEMS, and about 0.5% to about 2.5% of DMG-PEG2000 (in molar amounts). 119. The lipid particle of claim 118 or the method of claim 118, wherein the lipid particle comprises about 35% of SS-OP, about 15% of DODG, about 28.5% of cholesterol, about 20% CHEMS, and about 1.5% of DMG-PEG2000 (in molar amounts). 120. The lipid particle of claim 1 or the method of claim 2 or 3, wherein the lipid particle comprises about 25% to about 45% of SS-OP, about 5% to about 25% of DOPE, about 15% to about 35% of cholesterol, about 11% to about 30% CHEMS, and about 0.5% to about 2.5% of DMG-PEG2000 (in molar amounts). 121. The lipid particle of claim 121 or the method of claim 121, wherein the lipid particle comprises about 35% of SS-OP, about 15% of DOPE, about 28.5% of cholesterol, about 20% CHEMS, and about 1.5% of DMG-PEG2000 (in molar amounts). 122. The lipid particle of claim 1 or the method of claim 2 or 3, wherein the lipid particle comprises about 25% to about 45% of SS-OP, about 5% to about 25% of DODG, about 15% to about 35% of cholesterol, about 11% to about 30% CHEMS, and about 0.5% to about 2.5% of DMPE-PEG2000 (in molar amounts). 123. The lipid particle of claim 122 or the method of claim 122, wherein the lipid particle comprises about 35% of SS-OP, about 15% of DODG, about 28.5% of cholesterol, about 20% CHEMS, and about 1.5% of DMPE-PEG2000 (in molar amounts) 124. The lipid particle of claim 1 or the method of claim 2 or 3, wherein the lipid particle comprises about 25% to about 45% of SS-OP, about 5% to about 25% of DOPE, about 15% to about 35% of cholesterol, about 11% to about 30% CHEMS, and about 0.5% to about 2.5% of DMPE-PEG2000 (in molar amounts). 125. The lipid particle of claim 124 or the method of claim 124, wherein the lipid particle comprises about 35% of SS-OP, about 15% of DOPE, about 28.5% of cholesterol, about 20% CHEMS, and about 1.5% of DMPE-PEG2000 (in molar amounts) 126. The lipid particle of claim 1 or the method of claim 2 or 3, wherein the lipid particle comprises about 25% to about 45% of SS-OP, about 5% to about 25% of DODG, about 15% to about 35% of cholesterol, about 11% to about 30% CHEMS, and about 0.5% to about 2.5% of 18:1 PEG2000-PE (in molar amounts). 127. The lipid particle of claim 126 or the method of claim 126, wherein the lipid particle comprises about 35% of SS-OP, about 15% of DODG, about 28.5% of cholesterol, about 20% CHEMS, and about 1.5% of 18:1 PEG2000-PE (in molar amounts) 128. The lipid particle of claim 1 or the method of claim 2 or 3, wherein the lipid particle comprises about 25% to about 45% of SS-OP, about 5% to about 25% of DOPE, about 15% to about 35% of cholesterol, about 11% to about 30% CHEMS, and about 0.5% to about 2.5% of 18:1 PEG2000-PE (in molar amounts). 129. The lipid particle of claim 128 or the method of claim 128, wherein the lipid particle comprises about 35% of SS-OP, about 15% of DOPE, about 28.5% of cholesterol, about 20% CHEMS, and about 1.5% of 18:1 PEG2000-PE (in molar amounts). 130. The lipid particle of claim 1 or the method of claim 2 or 3, wherein the lipid particle comprises about 30% to about 50% of SS-OP, about 15% to about 55% of cholesterol, about 11% to about 30% CHEMS, and about 0.5% to about 2.5% of DMG-PEG2000 (in molar amounts). 131. The lipid particle of claim 130 or the method of claim 130, wherein the lipid particle comprises about 40% of SS-OP, about 38.5% of cholesterol, about 20% CHEMS, and about 1.5% of DMG-PEG2000 (in molar amounts). 132. The lipid particle of claim 1 or the method of claim 2 or 3, wherein the lipid particle comprises about 20% to about 45% of SS-OP, about 15% to about 55% of cholesterol, about 15% to about 35% CHEMS, and about 0.5% to about 2.5% of DMG-PEG2000 (in molar amounts). 133. The lipid particle of claim 132 or the method of claim 132, wherein the lipid particle comprises about 35% of SS-OP, about 38.5% of cholesterol, about 25% CHEMS, and about 1.5% of DMG-PEG2000 (in molar amounts). 134. The lipid particle of claim 1 or the method of claim 2 or 3, wherein the lipid particle comprises about 20% to about 40% of SS-OP, about 15% to about 55% of cholesterol, about 20% to about 40% CHEMS, and about 0.5% to about 2.5% of DMG-PEG2000 (in molar amounts). 135. The lipid particle of claim 134 or the method of claim 134, wherein the lipid particle comprises about 30% of SS-OP, about 38.5% of cholesterol, about 30% CHEMS, and about 1.5% of DMG-PEG2000 (in molar amounts). 136. The lipid particle of claim 1 or the method of claim 2 or 3, wherein the lipid particle comprises about 15% to about 35% of SS-OP, about 15% to about 55% of cholesterol, about 25% to about 45% CHEMS, and about 0.5% to about 2.5% of DMG-PEG2000 (in molar amounts). 137. The lipid particle of claim 136 or the method of claim 136, wherein the lipid particle comprises about 25% of SS-OP, about 38.5% of cholesterol, about 35% CHEMS, and about 1.5% of DMG-PEG2000 (in molar amounts). 138. The lipid particle of claim 1 or the method of claim 2 or 3, wherein the lipid particle comprises about 30% to about 50% of SS-OP, about 15% to about 55% of cholesterol, about 15% to about 35% CHEMS, and about 0.5% to about 2.5% of DMG-PEG2000 (in molar amounts). 139. The lipid particle of claim 138 or the method of claim 138, wherein the lipid particle comprises about 40% of SS-OP, about 33.5% of cholesterol, about 25% CHEMS, and about 1.5% of DMG-PEG2000 (in molar amounts). 140. The lipid particle of claim 1 or the method of claim 2 or 3, wherein the lipid particle comprises about 30% to about 50% of SS-OP, about 15% to about 55% of cholesterol, about 20% to about 40% CHEMS, and about 0.5% to about 2.5% of DMG-PEG2000 (in molar amounts). 141. The lipid particle of claim 140 or the method of claim 140, wherein the lipid particle comprises about 40% of SS-OP, about 28.5% of cholesterol, about 30% CHEMS, and about 1.5% of DMG-PEG2000 (in molar amounts). 142. A lipid particle comprising: a. one or more ionizable lipids in a molar amount of about 20% to about 70%; b. one or more neutral lipids in a molar amount of about 2.5% to about 25%; c. one or more sterols in a molar amount of about 20% to about 50%; d. one or more charged lipids in a molar amount of about 10% or less than 10%; and e. one or more stealth lipids in a molar amount of about 0.25% to about 3%. 143. The lipid particle of claim 142, wherein the one or more charged lipids in the lipid particle is selected from the group consisting of cholesteryl hemisuccinate (“CHEMS”), 1,2- distearoyl-3-trimethylammonium-propane (“DSTAP”), 18:11,2-dioleoyl-3-trimethylammonium- propane (“DOTAP”), 1,2-dioleoyl-sn-glycero-3-phosphate (“18:1 PA”), 18:11-stearoyl-2- oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (“18:1 PG”), phosphatidylglycerols, cardiolipins, diacylphosphatidylserines, diacylphosphatidic acids, N-dodecanoyl phosphatidylethanolamines, N-succinyl phosphatidylethanolamines, N-glutarylphosphatidylethanolamines, lysylphosphatidylglycerols, palmitoyloleyolphosphatidylglycerol (“POPG”), 1,2-dimyristoyl-3- trimethylammonium-propane (“DMTAP”), 1,2-dipalmitoyl-3-trimethylammonium-propane (“DPTAP”), palmitoyloleoyl-3-trimethylammonium-propane (“POTAP”), 1,2-dioleoyl-3- dimethylammonium-propane (“DODAP”), palmitoyloleoyl-3-dimethylammonium-propane (“PODAP”), 1,2-dimyristoyl-3-dimethylammonium-propane (“DMDAP”), 1,2-dipalmitoyl-3- dimethylammonium-propane (“DPDAP”), 1,2-distearoyl-3-dimethylammonium-propane (“DSDAP”), 1,2-dioleoyl-3-dimethylhydroxyethyl-ammonium-propane (“DODMHEAP”) (also known as DORI), palmitoyloleoyl-3-dimethylhydroxyethyl-ammonium-propane (“PODMHEAP”) (also known as PORI), 1,2-dimyristoyl-3-dimethylhydroxyethyl-ammonium- propane (“DMDMHEAP”) (also known as DMRI), 1,2-dipalmitoyl-3-dimethylhydroxyethyl- ammonium-pPropane (“DPDMHEAP”) (also known as DPRI), 1,2-distearoyl-3- dimethylhydroxyethyl-ammonium-propane “(DSDMHEAP”) (also known as DSRI), 1,2- iioleoyl-3-methylhydroxyethylammonium-propane “(DOMDHEAP”), palmitoyloleoyl-3- methylhydroxyethylammonium-propane (“POMDHEAP”), 1,2-dimyristoyl-3- methyldihydroxyethylammonium-propane (“DMMDHEAP”), 1,2-dipalmitoyl-3- methyldihydroxyethylammonium-propane (“DPMDHEAP”), 1,2-distearoyl-3- methyldihydroxyethylammonium-propane (“DSMDHEAP”), 1,2-dioleoyl-3- methyldihydroxyethylammonium-propane (“DOMHEAP”), palmitoyloleoyl-3- methylhydroxyethylammonium-propane (“POMHEAP”), 1,2-dimyristoyl-3- methylhydroxyethylammonium-propane (“DMMHEAP”), 1,2-dipalmitoyl-3- methylhydroxyethylammonium-propane (“DPMHEAP”), 1,2-distearoyl-3- methylhydroxyethylammonium-propane (“DSMHEAP”), 1,2-dioleoyl-3- dihydroxyethylammonium-propane (“DODHEAP”), palmitoyloleoyl-3- dihydroxyethylammonium-propane (“PODHEAP”), 1,2-dimyristoyl-3- dihydroxyethylammonium-propane (“DMDHEAP”), 1,2-dipalmitoyl-3- dihydroxyethylammonium-propane (“DPDHEAP”), 1,2-distearoyl-3-dihydroxyethylammonium- propane (“DSDHEAP”), dimethyldioctadecylammonium bromide (“DDAB”), dioleyldimethylammonium chloride (“DODAC”), 1,2-dioleoyl-sn-glycero-3- ethylphosphocholine (“DOEPC”), 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (“DMEPC”), 1,2-dipalmitoyl-sn-glycero-3-ethylphosphocholine (“DPEPC”), 1,2-distearoyl-sn- glycero-3-ethylphosphocholine (“DSEPC”), palmitoyloleoyl-sn-glycero-3-ethylphosphocholine (“POEPC”), 1,2-dioleyl-3-dimethyl-hydroxyethyl ammonium propane (“DORIE”), 1,2- dimyristyl-3-dimethyl-hydroxyethyl ammonium propane (“DMRIE”), 1,2-dioleoyl-3-methyl- (methoxycarbonyl-ethyl)ammonium-propane (“DOMCAP”), 1,2-dioleoyl-3-methyl- (methoxycarbonylmethyl)ammonium-propane (“DOMGME”), 1,2-dioleoyl-3-N-pyrrolidine- propane (“DOP5P”), 1,2-dioleoyl-3-N-pyrridinium-propane, bromide salt (“DOP6P”), 3b-[N- (N9,N9-dimethylaminoethane)carbamoyl] cholesterol (“DC-Chol”), 3b-[N-(N9,N9- trimethylaminoethane) carbamoyl] cholesterol (“TC-Chol”), 3b(N-(N,N'-Dimethylaminoethan)- carbamoyl)cholesterol (“DAC-Chol”), cholesteryl-oxycarbonyl-methyl-trimethylammonium chloride (“Chol-Betaine”), N-methyl{4-N-amino[(3'-β-cholesteryl) carbamoyl]}piperazine (“N- methyl-PipChol”), cetyltrimethylammonium bromide (“CTAB”), N-[1-(2,3-dioleyloxy)propyl]- N,N,N-trimethyl ammonium chloride (“DOTMA”), 4-(2-aminoethyl)-morpholino- cholesterolhemisuccinate: (“MoChol”), histaminyl-Cholesterolhemisuccinate (“HisChol”), cholesterol-(3-imidazol-1-yl propyl)carbamate (“Chim”), (N-2-propylamino[(3'-β-cholesteryl) carbamoyl]}morpholine (“MoC3Chol”), [(3-morpholine-4-yl-propylcarbamoyl)-methyl]- carbamic acid cholesteryl ester (“Chol-C3N-Mo3”), (“Chol-C3N-Mo2”), [(2-morpholine-4-yl- ethylcarbamoyl)methyl]-carbamic acid cholesteryl ester (“Chol-C4N-Mo2”), [1-methyl-2-(2- morpholine-4-yl-ethylcarbamoyl)-propyl]-carbamic acid cholesteryl ester (“Chol-DMC3N- Mo2”), 2-(2-morpholine-4-yl-ethylcarbamoyl)-cyclohexane carboxylic acid cholesteryl ester (“CholC4Hex-Mo2”), 4-(2-aminoethyl)-morpholino-cholesterol-2,3-dimethylhemisuccinate (“DmC4Mo2”), 4-(2-aminoethyl)-morpholino-cholesterol-2,2-dimethylhemimalonate (“DmC3Mo2”), 4-(2-aminoethyl)-morpholino-cholesterol-hemimalonate (“C3Mo2”), 4-(2- aminopropyl)-morpholino-cholesterol-hemimalonate (“C3Mo3”), 4-(2-aminoethyl)-morpholino- cholesterol-hemiglutarate (“C5Mo2”), 4-(2-aminoethyl)-morpholino-cholesterol-hemiadipate (“C6Mo2”), 4-(2-aminoethyl)-morpholino-cholesterol-hemiadipate (“C8Mo2”), 4-(2- aminobutyl)-morpholino-cholesterol-hemisuccinate (“C4Mo4”), 4{N-2-ethylamino[(3'-β- cholesteryl) carbamoyl]}piperazine (“PipC2Chol”), {N-2-ethylamino[(3'-β-cholesteryl) carbamoyl]}morpholine (“MoC2Chol”), {N-2-ethylamino[(3'-β-cholesteryl) carbamoyl]}pyrrolidine (“PyrroC2Chol”), {N-2-propylamino[(3'-β-cholesteryl) carbamoyl]}imidazole (“ImC3Chol”), {N-2-ethylamino[(3'-β-cholesteryl) carbamoyl]}pyridine (“PyC2Chol”), 1,2-dioleoyl-3-N-morpholine-propane (“MoDO”), 1,2-dipalmitoyl-3-N- morpholine-propane (“MoDP”), 4,(2,3-bis-acyloxy-propyl)-1-methyl-1H-imidazole (“DOIM”) (also known as DPIM). diacylglycerolhemisuccinate, e.g. dioctadecylamido-glycylspermine (“DOGS”), dimyristoylglycerolhemisuccinate (“DMGS”) (also known as DMG-Succ), 1- palmitoyl-2-oleoylglycerolhemisuccinate (“POGS”) (also known as POG-Succ), dipalmitoylglycerolhemisuccinate (“DPGS”) (also known as POG-Succ), distearoylglycerolhemisuccinate (“DSGS”) (also known as DSG-Succ), diacylglycerolhemimalonate, e.g. dioleoylglycerolhemimalonate (“DOGM”), dimyristoylglycerolhemimalonate (“DMGM”), diacylglycerolhemiglutarate, e.g. dioleoylglycerolhemiglutarate (“DOGG”), dimyristoylglycerolhemiglutarate (“DMGG”), diacylglycerolhemiadipate, e.g. dioleoylglycerolhemiadipate (“DOGA”), dimyristoylglycerolhemiadipate (“DMGA”), diacylglycerolhemicyclohexane-1,4-dicarboxylic acid, e.g. dioleoylglycerolhemicyclohexane-1,4-dicarboxylic acid (“DO-cHA”), dimyristoylglycerolhemicyclohexane-1,4-dicarboxylic acid (“DM-cHA”), (2,3-Diacyl- propyl)amino}-oxoalkanoic acid, e.g.4-{(2,3-dioleoyl-propyl)amino}-4-oxobutanoic acid (“DOAS”), 3-{(2,3-dioleoyl-propyl)amino}-3-oxopropanoic acid (“DOAM”), 5-{(2,3-dioleoyl- propyl)amino}-5-oxopentanoic acid (“DOAG”), 6-{(2,3-dioleoyl-propyl)amino}-6-oxohexanoic acid (“DOAA”), 4-{(2,3-dimyristoyl-propyl)amino}-4-oxobutanoic acid (“DMAS”), 3-{(2,3- dimyristoyl-propyl)amino}-3-oxopropanoic acid (“DMAM”), 5-{(2,3-dimyristoyl- propyl)amino}-5-oxopentanoic acid (“DMAG”), 6-{(2,3-dimyristoyl-propyl)amino}-6- oxohexanoic acid (“DMAA”), diacyl-alkanoic acid, e.g.2,3-dioleoyl-propanoic acid (“DOP”), 3,4-dioleoyl-butanoic acid (“DOB”), 5,6-dioleoyl-hexanoic acid (“DOS”), 4,5-dioleoyl-pentanoic acid (“DOM”), 6,7-dioleoyl-heptanoic acid (“DOG”), 7,8-dioleoyl-octanoic acid (“DOA”), 2,3- dimyristoyl-propanoic acid (“DMP”), 3,4-dioleoyl-butanoic acid (“DOB”), 5,6-dimyristoyl- hexanoic acid (“DMS”), 4,5-dimyristoyl-pentanoic acid (“DMM”), 6,7-dimyristoyl-heptanoic acid (“DMG”), 7,8-dimyristoyl-octanoic acid (“DMA”), cholesteryloxycarbonylaminocarboxylic acid, e.g. cholesterolhemidodecane dicarboxylic acid (“Chol-C12”), 12- cholesteryloxycarbonylaminododecanoic acid (“CholC13N”), fatty acids, e.g. oleic acid, myristic acid, palmitic acid, stearic acid, nervonic acid, behenic acid, dioleoylphosphatidic acid (“DOPA”), 1,2-dimyristoyl-sn-glycero-3-phosphate (“DMPA”), 1,2-dipalmitoyl-sn-glycero-3- phosphate (“DPPA”), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphate (“POPA”), 1,2-Distearoyl- sn-glycero-3-phosphate (“DSPA”), cholesterol sulphate (“Chol-SO4”), dioleoylphosphatidylglycerol (“DOPG”), 1,2-dimyristoyl-sn-glycero-3-phospho-(1'-rac- glycerol), (“DMPG”), dipalmitoylphosphatidylglycerol (“DPPG”), 1-palmitoyl-2-oleoyl-sn- glycero-3-phosphoglycerol (“POPG”), 1,2-distearoyl-sn-glycero-3-phospho-rac-glycerol (“DSPG”), dioleoylphosphatidylserine (“DOPS”), 1,2-dimyristoyl-sn-glycero-3-phospho-L- serine (“DMPS”), dipalmitoylphosphatidylserine (“DPPS”), 1-palmitoyl-2-oleoyl-sn-glycero-3- phospho-L-serine (“POPS”), 1,2-distearoyl-sn-glycero-3-phospho-L-serine (“DSPS”), or cetyl- phosphate. 144. The lipid particle of claim 142, wherein the one or more charged lipids in the lipid particle is selected from the group consisting of cholesteryl hemisuccinate (“CHEMS”), 1,2- distearoyl-3-trimethylammonium-propane (“DSTAP”), 18:11,2-dioleoyl-3-trimethylammonium- propane (“DOTAP”), 1,2-dioleoyl-sn-glycero-3-phosphate (“18:1 PA”), 18:11-stearoyl-2- oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (“18:1 PG”), phosphatidylglycerols, cardiolipins, diacylphosphatidylserines, diacylphosphatidic acids, N-dodecanoyl phosphatidylethanolamines, N-succinyl phosphatidylethanolamines, N-glutarylphosphatidylethanolamines, lysylphosphatidylglycerols, and palmitoyloleyolphosphatidylglycerol (“POPG”). 145. The lipid particle of any one of claims 142-144, wherein only one charged lipid is in the lipid particle. 146. The lipid particle of claim 145, wherein the only charged lipid in the lipid particle is CHEMS. 147. The lipid particle of any one of claims 142-146, wherein the one or more charged lipids in the lipid particle are in a molar of about 10%, less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, or less than 0.1%. 148. The lipid particle of any one of claims 142-146, wherein the one or more charged lipids in the lipid particle are in a molar amount of about 1% to about 10%, about 1% to about 9%, about 1% to about 8%, about 1% to about 7%, about 1% to about 6%, about 1% to about 5%, about 1% to about 4%, about 1% to about 3%, about 1% to about 2%, about 2% to about 10%, about 2% to about 9%, about 2% to about 8%, about 2% to about 7%, about 2% to about 6%, about 2% to about 5%, about 2% to about 4%, about 2% to about 3%, about 3% to about 10%, about 3% to about 9%, about 3% to about 8%, about 3% to about 7%, about 3% to about 6%, about 3% to about 5%, about 3% to about 4%, about 4% to about 10%, about 4% to about 9%, about 4% to about 8%, about 4% to about 7%, about 4% to about 6%, about 4% to about 5%, about 5% to about 10%, about 5% to about 9%, about 5% to about 8%, about 5% to about 7%, or about 5% to about 6%. 149. The lipid particle of claim 142-146, wherein the one or more charged lipids in the lipid particle are in a molar amount of about 10%. 150. The lipid particle of claim 142, which does not comprise a charged lipid. 151. The lipid particle of any one of claims 142-150, further comprising a payload. 152. A method of targeting a payload to a tissue other than a spleen of a subject in vivo comprising combining a lipid particle or a composition comprising the payload encapsulated within a lipid particle or a composition comprising one or more ionizable lipids, one or more neutral lipids, one or more sterols, one or more stealth lipids, and/or one or more charged lipids, wherein the lipid particle or composition does not comprise CHEMS or comprises a molar amount of about 10% or less than 10% of CHEMS. 153. The method of claim 152, wherein the CHEMS is in a molar of about 10%, less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2%, less than 1%, or less than 0.1%. 154. The method of claim 152, wherein the CHEMS is in a molar amount of about 1% to about 10%, about 1% to about 9%, about 1% to about 8%, about 1% to about 7%, about 1% to about 6%, about 1% to about 5%, about 1% to about 4%, about 1% to about 3%, about 1% to about 2%, about 2% to about 10%, about 2% to about 9%, about 2% to about 8%, about 2% to about 7%, about 2% to about 6%, about 2% to about 5%, about 2% to about 4%, about 2% to about 3%, about 3% to about 10%, about 3% to about 9%, about 3% to about 8%, about 3% to about 7%, about 3% to about 6%, about 3% to about 5%, about 3% to about 4%, about 4% to about 10%, about 4% to about 9%, about 4% to about 8%, about 4% to about 7%, about 4% to about 6%, about 4% to about 5%, about 5% to about 10%, about 5% to about 9%, about 5% to about 8%, about 5% to about 7%, or about 5% to about 6%. 155. The method of claim 152, wherein the CHEMS is in a molar amount of about 10%. 156. The method of claim 152, which does not comprise CHEMS. 157. The method of any one of claims 152-156, wherein the one or more ionizable lipids are in a molar amount of about 20% to about 70%. 158. The method of any one of claims 152-157, wherein the one or more neutral lipids are in a molar amount of about 2.5% to about 25%. 159. The method of any one of claims 152-158, wherein the one or more sterols is in a molar amount of about 20% to about 50%. 160. The method of any one of claims 152-159, wherein the one or more stealth lipids are in a molar amount of about 0.25% to about 3%. 161. The lipid particle of any one of claims 1142-151 or the method of any one of claims 148- 156, wherein the lipid particle delivers the payload to the liver. 162. The lipid particle of claim 161 or the method of claim 161, wherein the ratio of the payload delivered to the liver versus is spleen is greater than 1.1. 163. The lipid particle of claim 161 or the method of claim 161, wherein the ratio of the payload delivered to the liver versus spleen is about 1.1 to about 12. 164. The lipid particle of any one of claims 142-151 and 161-163 or the method of any one of claims 152-163, wherein the ratio of payload delivered to the spleen versus liver is determined using an imaging system. 165. The lipid particle of a claim 164 or the method of claim 164, wherein the imaging system is a LICOR Pearl Trilogy imaging system using Image Studio software from LICOR version 5.2.5. 166. The lipid particle of any one of claims 142-151 and 161-165 or the method of any one of claims 152-166, wherein the lipid particles comprise one or more ionizable lipids. 167. The lipid particle of claim 166 or the method of claim 166, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 25% to about 65%, about 30% to about 65%, about 35% to about 65%, about 45% to about 65%, about 50% to about 65%, about 25% to about 60%, about 30% to about 60%, about 35% to about 60%, about 45% to about 60%, about 50% to about 60%, about 25% to about 55%, about 30% to about 55%, about 35% to about 55%, about 45% to about 55%, about 50% to about 55%, about 25% to about 50%, about 30% to about 50%, about 35% to about 50%, or about 45% to about 50%. 168. The lipid particle of claim 166 or the method of claim 166, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, or about 65%. 169. The lipid particle of claim 166 or the method of claim 166, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 30% to about 60%. 170. The lipid particle of claim 166 or the method of claim 166, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 40% to about 60%. 171. The lipid particle of a claim 166 or the method of claim 166, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 40% to about 50%. 172. The lipid particle of claim 166 or the method of claim 166, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 50% to about 60%. 173. The lipid particle of claim 166 or the method of claim 166, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 30%. 174. The lipid particle of claim 166 or the method of claim 166, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 40%. 175. The lipid particle of claim 166 or the method of claim 166, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 50%. 176. The lipid particle of claim 166 or the method of claim 166, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 55%. 177. The lipid particle of claim 166 or the method of claim 166, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 60%. 178. The lipid particle of claim 166 or the method of claim 166, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 65%. 179. The lipid particle of claim 166 or the method of claim 166, wherein the one or more ionizable lipids in the lipid particle are in a molar amount of about 70%. 180. The lipid particle of any one of claims 166-179 or the method of any one claims 166-179, wherein the one or more ionizable lipids in the lipid particles are one or more selected from the group consisting of DLin-MC3-DMA (“MC3”), DLin-KC2-DMA (“KC2”), ssPalmO-Phe (“SS- OP”), C12-200, SM-102, α-D-tocopherolsuccinoyl (“SS-EC”), ALC-0315 (“ALC”), Tri-N- tridecyl 3-(ethyl(methyl)amino)propanoate (“304-O13”), tetrakis(2-(octyldisulfaneyl)ethyl) 3,3',3'',3'''-(((methylazanediyl)bis(propane-3,1-diyl))bis(azanetriyl))tetrapropionate (“306- O12B”), 9-[4-(dimethylamino)-1-oxobutoxy]-heptadecanedioic acid, 1,17-di-(2Z)-2-nonen-1-yl ester (“L319”), 9,12-octadecadienoic acid, (9Z,12Z)-1,1′,1′′,1′′′-[(3,6-dioxo-2,5- piperazinediyl)bis(4,1-butanediylnitrilodi-4,1-butanediyl)] ester (“OF-C4-Deg-Lin”), 2- (dioctylamino)ethyl nonyl hydrogen phosphate (“9A1P9”), 5-(((3- (dibutylamino)propyl)amino)methyl)-6-hydroxyundecane-1,11-diyl (9Z,9'Z,12Z,12'Z)- bis(octadeca-9,12-dienoate) (“IR-117-17”), 9Z,12Z-octadecadienoic acid, 3-[4,4-bis(octyloxy)-1- oxobutoxy]-2-[[[[3-(diethylamino)propoxy]carbonyl]oxy]methyl]propyl ester (“LP-01”) and 4A3-SC8 181. The lipid particle of any one of claims 166-179 or the method of any one of claims 166- 179, wherein the one or more ionizable lipids in the lipid particle are one or more selected from the group consisting of DLin-MC3-DMA (“MC3”), DLin-KC2-DMA (“KC2”), ssPalmO-Phe ("SS-OP"), C12-200, SM-102, α-D-tocopherolsuccinoyl (“SS-EC”), and ALC-0315 (“ALC”). 182. The lipid particle of claim 181 or the method of claim 181, wherein the one or more ionizable lipids in the lipid particle are one or more selected from the group consisting of ssPalmO-Phe ("SS-OP"), C12-200, SM-102, and ALC-0315 (“ALC”). 183. The lipid particle of any one of claims 166-182 or the method of any one of claims 166- 182, wherein only one ionizable lipid is in the lipid particle. 184. The lipid particle of claim 183 or the method of claim 183, wherein the only ionizable lipid in the lipid particle is SS-OP. 185. The lipid particle of claim 183 or 184 or the method of claim 183 or 184, wherein when administered to a subject in need thereof, the subject exhibits one or more of: (i) an increase in Treg cells, (ii) reduction in effector T cells, (iii) reduction in B-cells, (iv) reduction in cytokine production, (v) reduction in activated B cells; (vi) reduction in activated effector T cells; or (vii) any combination thereof. 186. The lipid particle of claim 183 or 184 or the method of claim 183 or 184, which when administered to a subject in need thereof, reduces B-cell levels in the subject. 187. The lipid particle of claim 183 or 184 or the method of claim 183 or 184, which when administered to a subject in need thereof, reduces B-cell levels in the subject as compared with a reference lipid particle containing an ionizable lipid other than SS-OP. 188. The lipid particle of claim 183 or 184 or the method of claim 183 or 184, which when administered to a subject in need thereof, reduces B-cell levels in the subject as compared with a reference lipid particle containing MC-3 as the ionizable lipid. 189. The lipid particle of any one of claims 183-188 or the method of any one of claims 183- 188, which when administered to a subject in need thereof, reduces T-cell levels in the subject. 190. The lipid particle of any one of claims 183-188 or the method of any one of claims 183- 188, which when administered to a subject in need thereof, reduces T-cell levels in the subject as compared with a reference lipid particle containing an ionizable lipid other than SS-OP. 191. The lipid particle of any one of claims 183-188 or the method of any one of claims 183- 188, which when administered to a subject in need thereof, reduces T-cell levels in the subject as compared with a reference lipid particle containing MC-3 as the ionizable lipid. 192. The lipid particle of any one of claims 183-191 or the method of any one of claims 183- 191, which when administered to a subject in need thereof, reduces levels of IFN-α in the subject. 193. The lipid particle of any one of claims 183-191 or the method of any one of claims 183- 191, which when administered to a subject in need thereof, reduces levels of IFN-α in the subject as compared with a reference lipid particle containing an ionizable lipid other than SS-OP 194. The lipid particle of any one of claims 183-191 or the method of any one of claims 183- 191, which when administered to a subject in need thereof, reduces levels of IFN-α in the subject as compared with a reference lipid particle containing MC-3 as the ionizable lipid. 195. The lipid particle of any one of claims 166-179 or the method of any one of claims 166- 179, wherein the one or more ionizable lipids in the lipid particle comprises α-D- tocopherolsuccinoyl (“SS-EC”). 196. The lipid particle of claim 195 or the method of claim 195, which when administered to a subject in need thereof, increases B-cell levels in the subject. 197. The lipid particle of claim 195 or the method of claim 195, which when administered to a subject in need thereof, increases B-cell levels in the subject as compared with a reference lipid particle containing an ionizable lipid other than SS-EC. 198. The lipid particle of claim 195 or the method of claim 195, which when administered to a subject in need thereof, increases B-cell levels in the subject as compared with a reference lipid particle containing MC-3 as the ionizable lipid. 199. The lipid particle of any one of claims 195-198 or the method of any one of claims 190- 193, which when administered to a subject in need thereof, increases T-cell levels in the subject. 200. The lipid particle of any one of claims 195-198 or the method of any one of claims 190- 193, which when administered to a subject in need thereof, increases T-cell levels in the subject as compared with a reference lipid particle containing an ionizable lipid other than SS-EC. 201. The lipid particle of any one of claims 195-198 or the method of any one of claims 190- 193, which when administered to a subject in need thereof, increases T-cell levels in the subject as compared with a reference lipid particle containing MC-3 as the ionizable lipid. 202. The lipid particle of any one of claims 195-201 or the method of any one of claims 190- 196, which when administered to a subject in need thereof, increases levels of IFN-α in the subject. 203. The lipid particle of any one of claims 195-201 or the method of any one of claims 190- 196, which when administered to a subject in need thereof, increases levels of IFN-α in the subject as compared with a reference lipid particle containing an ionizable lipid other than SS- EC. 204. The lipid particle of any one of claims 195-201 or the method of any one of claims 190- 196, which when administered to a subject in need thereof, increases levels of IFN-α in the subject as compared with a reference lipid particle containing MC-3 as the ionizable lipid. 205. The lipid particle of any one of claims 142-151 and 161-203 or the method of any one of claims 148-199, wherein the lipid particle comprises one or more neutral lipids. 206. The lipid particle of claim 205 or the method of claim 205, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 2.5% to about 20%, about 2.5% to about 17.5%, about 2.5% to about 15%, about 2.5% to about 12.5%, about 2.5% to about 10%, about 5% to about 25%, about 5% to about 20%, about 5% to about 17.5%, about 5% to about 15%, about 5% to about 12.5%, about 5% to about 10%, about 7.5% to about 25%, about 7.5% to about 20%, about 7.5% to about 17.5%, about 7.5% to about 15%, about 7.5% to about 12.5%, about 7.5% to about 10%, about 10% to about 25%, about 10% to about 20%, about 10% to about 17.5%, about 10% to about 15%, about 10% to about 12.5%, about 12.5% to about 25%, about 12.5% to about 20%, about 12.5% to about 17.5%, or about 12.5% to about 15%. 207. The lipid particle of claim 205 or the method of claim 205, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 5%, about 7.5%, about 10%, about 12.5%, about 15%, about 17.5%, about 20%, about 22.5%, or about 25%. 208. The lipid particle of claim 205 or the method of claim 205, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 5% to about 20%. 209. The lipid particle of claim 205 or the method of claim 205, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 7.5% to about 17.5%. 210. The lipid particle of claim 205 or the method of claim 205, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 2.5%. 211. The lipid particle of claim 205 or the method of claim 205, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 5%. 212. The lipid particle of claim 205 or the method of claim 205, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 7.5%. 213. The lipid particle of claim 205 or the method of claim 205, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 10%. 214. The lipid particle of claim 205 or the method of claim 205, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 12.5%. 215. The lipid particle of claim 205 or the method of claim 205, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 15%. 216. The lipid particle of claim 205 or the method of claim 205, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 17.5%. 217. The lipid particle of claim 205 or the method of claim 205, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 20%. 218. The lipid particle of claim 205 or the method of claim 205, wherein the one or more neutral lipids in the lipid particle are in a molar amount of about 25%. 219. The lipid particle of any one of claims 205-218 or the method of any one of claims 205- 218, wherein the one or more neutral lipids in the lipid particles are one or more phosphatidylcholine (“PC”), phosphatidylethanolamine (“PE”), and combination thereof 220. The lipid particle of any one of claims 205-218 or the method of any one of claims 205- 218, wherein the one or more neutral lipids in the lipid particle are one or more selected from the group consisting of wherein the one or more neutral lipids in the lipid particle are one or more selected from the group consisting of 1,2-diastearoyl-sn-glycero-3-phosphocholine ("DSPC"), 1,2-dioleoyl-sn-glycero-3-phosphocholine (“DOPC”), 1,2- dioctadecanoyl-sn-glycerol (“DSDG”), 1-2-dioleoyl-sn-glycerol, 1-2-di-(9Z-octadecenoyl)-sn-glycerol ("DODG"), 1,2- dioleoyl-sn-glycero-3-phosphoethanolamine ("DOPE"), diacylphosphatidylcholine, diacylphosphatidylethanolamine, ceramide, sphingomyelin, cephalin, cerebrosides, diacylglycerols dipalmitoylphosphatidylcholine (“DPPC”), palmitoyloleoyl-phosphatidylcholine (“POPC”), palmitoyloleoyl-phosphatidylethanolamine (“POPE”), palmitoyloleyol- phosphatidylglycerol (POPG), dipalmitoyl-phosphatidylethanolamine (“DPPE”), dimyristoyl- phosphatidylethanolamine (“DMPE”), distearoyl-phosphatidylethanolamine (“DSPE”), monomethyl-phosphatidylethanolamine, dimethyl-phosphatidylethanolamine, dielaidoyl- phosphatidylethanolamine (“DEPE”), stearoyloleoyl-phosphatidylethanolamine (“SOPE”), and egg phosphatidylcholine (“EPC”). 221. The lipid particle of any one of claims 205-220 or the method of any one of claims 205- 220, wherein the one or more neutral lipids in the lipid particle are DOPE, DODG, or a combination thereof. 222. The lipid particle of any one of claims 205-2221 or the method of any one of claims 205- 2221, wherein only one neutral lipid is in the lipid particle. 223. The lipid particle of claim 222 or the method of claim 222, wherein the only neutral lipid in the lipid particle is DOPE. 224. The lipid particle of claim 222 or the method of claim 222, wherein the only neutral lipid in the lipid particle is DODG. 225. The lipid particle of any one of claims 142-151 and 161-224 or the method of any one of claims 152-2224, wherein the lipid particle comprises one or more sterols. 226. The lipid particle of claim 225 or the method of claim 225, wherein the one or more sterols in the lipid particle are in a molar amount of about 20% to about 45%, about 25% to about 45%, about 30% to about 45%, about 35% to about 45%, about 40% to about 45%, about 20% to about 40%, about 25% to about 40%, about 30% to about 40%, about 35% to about 40%, about 20% to about 30%, about 25% to about 30%, or about 20% to about 25%. 227. The lipid particle of claim 2225 or the method of claim 225, wherein the one or more sterols in the lipid particle are in a molar amount of about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, or about 50%. 228. The lipid particle of claim 225 or the method of claim 225, wherein the one or more sterols in the lipid particle are in a molar amount of about 20% to about 40%. 229. The lipid particle of claim 225 or the method of claim 225, wherein the one or more sterols in the lipid particle are in a molar amount of about 20% to about 30%. 230. The lipid particle of claim 225 or the method of claim 225, wherein the one or more sterols in the lipid particle are in a molar amount of about 30% to about 40%. 231. The lipid particle of claim 225 or the method of claim 225, wherein the one or more sterols in the lipid particle are in a molar amount of about 20%. 232. The lipid particle of claim 225 or the method of claim 225, wherein the one or more sterols in the lipid particle are in a molar amount of about 28.5%. 233. The lipid particle of claim 225 or the method of claim 225, wherein the one or more sterols in the lipid particle are in a molar amount of about 30%. 234. The lipid particle of claim 225 or the method of claim 225, wherein the one or more sterols in the lipid particle are in a molar amount of about 38.5%. 235. The lipid particle of claim 225 or the method of claim 225, wherein the one or more sterols in the lipid particle are in a molar amount of about 40%. 236. The lipid particle of any one of claims 225-235 or the method of any one of claims 225- 235 wherein the one or more sterols are cholesterol, β-sitosterol, stigmasterol, campesterol, fucosterol, brassicasterol, ergosterol, 9,11-dehydroergosterol, daucosterol, β-sitosterol acetate, and other C-24 alkyl derivatives, or combinations thereof. 237. The lipid particle of any one of claims 225-236 or the method of any one of claims 225- 236, wherein the one or more sterols are cholesterol, β-sitosterol, or combinations thereof. 238. The lipid particle of any one of claims 225-236 or the method of any one of claims 219- 230, wherein only sterol is in the lipid particle. 239. The lipid particle of claim 238 or the method of claim 238, wherein the only sterol in the lipid particle is cholesterol. 240. The lipid particle of any one of claims 225-239 or the method of any one of claims 193- 206, wherein the one or stealth lipids in the lipid particle are in a molar amount of about 0.5% to about 3%, about 1% to about 3%, about 1.5% to about 3%, about 2% to about 3%, about 2.5% to about 3%, about 0.25% to about 2.5%, about 0.5% to about 2.5%, about 1% to about 2.5%, about 1.5% to about 2.5%, about 2% to about 2.5%, about 0.25% to about 2%, about 0.5% to about 2%, about 1% to about 2%, about 1.5% to about 2%, about 0.25% to about 1.5%, about 0.5% to about 1.5%, or about 1% to about 1.5%. 241. The lipid particle of any one of claims 225-239 or the method of any one of claims 193- 206, wherein the one or more stealth lipids in the lipid particle are in a molar amount of about 1% to about 3%. 242. The lipid particle of any one of claims 225-239 or the method of any one of claims 193- 206, wherein the one or more stealth lipids in the lipid particle are in a molar amount of about 0.5%, about 1%, about 1.5%, about 2%, about 2.5%, or about 3%. 243. The lipid particle of any one of claims 225-239 or the method of any one of claims 193- 206, wherein the one or more stealth lipids in the lipid particle are in a molar amount of about 1%. 244. The lipid particle of any one of claims 225-239 or the method of any one of claims 193- 206, wherein the one or more stealth lipids in the lipid particle are in a molar amount of about 1.5%. 245. The lipid particle of any one of claims 225-239 or the method of any one of claims 193- 206, wherein the one or more stealth lipids in the lipid particle are in a molar amount of about 2%. 246. The lipid particle of any one of claims 225-239 or the method of any one of claims 193- 206, wherein the one or more stealth lipids in the lipid particle are in a molar amount of about 2.5% 247. The lipid particle of any one of claims 225-239 or the method of any one of claims 193- 206, wherein the one or more stealth lipids in the lipid particle are in a molar amount of about 3%. 248. The lipid particle of any one of claims 225-247 or the method of any one of claims 219- 240, wherein the one or more stealth lipids are one or more PEG terminated lipids, one or more polysarcosine derivatives, or combinations thereof. 249. The lipid particle of claim 248 or the method of claim 248, wherein the one or more stealth lipids are one or more PEG terminated lipids. 250. The lipid particle of claim 248 or 249 or the method of claim 248 or 249, wherein the one or more PEG terminated lipids in the lipid particle are one or more selected from the group consisting of 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 ("DMG- PEG2000"), distearoyl-rac-glycerol-PEG2K (“DSG-PEG2k”), [(2R)-2,3- di(octadecanoyloxy)propyl] 2-(2-methoxyethoxycarbonylamino)ethyl phosphate ("C18- mPEG2000"), [3-[3-(2-methoxyethoxy)propylcarbamoyloxy]-2-tetradecanoyloxypropyl] tetradecanoate (“PEG2000-c-DMG”), 3-[hydroxy-[2-[2-(2- methoxyethoxy)ethylamino]ethoxy]phosphoryl]oxy-2-tetradecanoyloxypropyl] tetradecanoate ("DMPE-PEG2000"), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] ("18:1 PEG2000-PE"), 1,2-distearoyl-sn-glycero-3- phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] ("DSPE-PEG2000-COOH), and Bis(1,2-distearoyl-sn-glycero-3-phosphoethanolamine)-N-[(polyethylene glycol)-2000] ("Bis- DSPE-PEG2000"). 251. The lipid particle of any one of claims 248-250 or the method of any one of claims 241- 243, wherein the one or more PEG terminated lipids in the lipid particle is DMG-PEG2000, DMPE-PEG2000, or a combination thereof. 252. The lipid particle of any one of claims 248-251 or the method of any one of claims 241- 244, wherein only one PEG terminated lipid is in the lipid particle. 253. The lipid particle of claim 245 or the method of claim 252, wherein the only PEG terminated lipid in the lipid particle is DMG-PEG2000. 254. The lipid particle of claim 245 or the method of claim 252, wherein the only PEG terminated lipid in the lipid particle is DMPE-PEG2000. 255. The lipid particle of claim 245 or the method of claim 252, wherein the only PEG terminated lipid in the lipid particle is PEG2000-PE. 256. The lipid particle of claim 241 or the method of claim 248, wherein the one or more stealth lipids are one or more polysarcosine derivative. 257. The lipid particle of claim 249 or the method of claim 256, wherein the one or more polysarcosine derivatives in the lipid particle are one or more selected from the group consisting of N-tetradecyl-polysarcosine-25 (“N-tetradecyl-pSar25”), N-hexadecyl-polysarcosine-25 (“N- hexadecyl-pSar25”), N-octadecyl-polysarcosine-25, N-dodecyl-polysarcosine-25 (“N-octadecyl- pSar25”), 1,2-dimyristoyl-sn-glycero-3-succinyl-N-polysarcosine-25 (“DMG-pSar25”), 1,2- dioleoyl-sn-glycero-3-phosphoethanolamine-N-polysarcosine-25 (ammonium salt) (“18:1 PE (DOPE), N,N-ditetradecylamine-N-succinyl[methyl(polysarcosine)45] (“N-TETAMINE- pSar45”), N,N-ditetradecylamine-N-succinyl[methyl(polysarcosine)35] (“N-TETAMINE- pSar35”), N,N-ditetradecyl-polysarcosine-25 (“N-TETAMINE-pSar25”), N-TETAMINE- pSar45-maleimide, or N-TETAMINE-PEOZ-40. 258. The lipid particle of claim 256 or 257 or the method of claim 256 or 257, wherein only one polysarcosine derivative is in the lipid particle. 259. The lipid particle of claim 142 or the method of claim 152, wherein the lipid particle comprises about 40% to about 60% of SS-OP, about 1% to about 20% of DODG, about 25% to about 45% of cholesterol, about 1% to about 10% of CHEMS, and about 0.5% to about 2.5% of DMG-PEG2000 (in molar amounts). 260. The lipid particle of claim 259 or the method of claim 259, wherein the lipid particle comprises about 50% of SS-OP, about 10% of DODG, about 38.5% of cholesterol, about 10% of CHEMS, and about 1.5% of DMG-PEG2000 (in molar amounts). 261. The lipid particle of claim 142 or the method of claim 152 comprising about 40% to about 60% of SS-OP, about 1% to about 20% of DODG, about 25% to about 45% of cholesterol, and about 0.5% to about 2.5% of DMG-PEG2000 (in molar amounts). 262. The lipid particle of claim 261 or the method of claim 261, wherein the lipid particle comprises about 50% of SS-OP, about 10% of DODG, about 38.5% of cholesterol, and about 1.5% of DMG-PEG2000 (in molar amounts). 263. A method of targeting a payload to the pancreas of a subject in need thereof comprising intraperitoneally administering the lipid particle of any one of claims 1, 4-151, and 162-262 to the subject. 264. A method of targeting a payload to a lymph node of a subject in need thereof comprising subcutaneously administering the lipid particle of any one of claims 1, 4-151, and 162-262 to the subject. 265. The lipid particle of any one of claims 1, 4-151, and 162-262 or the method of any one of claims 2-138 and 148-255, wherein the payload comprises a biologically active molecule. 266. The lipid particle of claim 265 or the method of claim 265, wherein the biologically active molecule is a small molecule, a nucleic acid, an aptamer, or any combination thereof. 267. The lipid particle of claim 265 or the method of claim 265, wherein the biologically active molecule comprises a nucleic acid. 268. The lipid particle of claim 267 or the method of claim 267, wherein the nucleic acid comprises a small interfering ribonucleic acid (siRNA), a short hairpin RNA (shRNA), a micro- ribonucleic acid (miRNA), a primary micro-ribonucleic acid (pri-miRNA), a long non-coding RNA (lncRNA), a messenger ribonucleic acid (mRNA), a clustered regularly interspaced short palindromic repeats (CRISPR) related nucleic acid, a CRISPR-RNA (crRNA), a single guide ribonucleic acid (sgRNA), a trans-activating CRISPR ribonucleic acid (tracrRNA), a plasmid deoxyribonucleic acid (pDNA), a transfer ribonucleic acid (tRNA), an antisense oligonucleotide (ASO), an antisense ribonucleic acid (RNA), a guide ribonucleic acid, deoxyribonucleic acid (DNA), a double stranded deoxyribonucleic acid (dsDNA), a single stranded deoxyribonucleic acid (ssDNA), a single stranded ribonucleic acid (ssRNA), a double stranded ribonucleic acid (dsRNA), a CRISPR-associated (Cas) protein, or combinations thereof. 269. The lipid particle of claim 268 or the method of claim 268, wherein the nucleic acid in the lipid particle comprises mRNA. 270. The lipid particle of claim 268 or the method of claim 268, wherein the nucleic acid in the lipid particle encodes a peptide having therapeutic activity. 271. The lipid particle of claim 270 or the method of claim 270, wherein the peptide comprises an epitope amino acid sequence. 272. The lipid particle of claim 270 or the method of claim 270, wherein the peptide induces immune tolerance to cells. 273. A nucleic acid-lipid particle comprising the lipid particle of any one of claims 1, 4-151, and 162-262 and a nucleic acid. 274. A composition comprising the lipid particle of any one of claims 1, 4-151, and 162-262. 275. A pharmaceutical composition comprising the lipid particle of any one of claims 1, 4-151, and 162-262 and one or more pharmaceutically acceptable carriers. 276. The pharmaceutical composition of claim 275, wherein one of the pharmaceutically acceptable carrier is sucrose. 277. The pharmaceutical composition of claim 275 or 276, wherein one of the pharmaceutically acceptable carrier is saline. 278. The pharmaceutical composition of claim 277, wherein the saline is buffered with tris. 279. The pharmaceutical composition of any one of claims 275-278, wherein the pharmaceutical composition is stored at -80 °C. 280. The pharmaceutical composition of any one of claims 275-278, wherein the pharmaceutical composition is stored at 4 °C. 281. A method of producing a nucleic acid-lipid particle, comprising mixing a nucleic acid with the lipid particle of any one of claims 1, 4-151, and 162-262. 282. The method of claim 281, wherein the nucleic acid comprises a small interfering ribonucleic acid (siRNA), a short hairpin RNA (shRNA), a micro-ribonucleic acid (miRNA), a primary micro-ribonucleic acid (pri-miRNA), a long non-coding RNA (lncRNA), a messenger ribonucleic acid (mRNA), a clustered regularly interspaced short palindromic repeats (CRISPR) related nucleic acid, a CRISPR-RNA (crRNA), a single guide ribonucleic acid (sgRNA), a trans- activating CRISPR ribonucleic acid (tracrRNA), a plasmid deoxyribonucleic acid (pDNA), a transfer ribonucleic acid (tRNA), an antisense oligonucleotide (ASO), an antisense ribonucleic acid (RNA), a guide ribonucleic acid, deoxyribonucleic acid (DNA), a double stranded deoxyribonucleic acid (dsDNA), a single stranded deoxyribonucleic acid (ssDNA), a single stranded ribonucleic acid (ssRNA), a double stranded ribonucleic acid (dsRNA), a CRISPR- associated (Cas) protein, or combinations thereof. 283. The method of claim 282, wherein the nucleic acid comprises mRNA. 284. The method of claim 282, wherein the nucleic acid encodes a peptide having therapeutic activity. 285. The method of claim 284, wherein the peptide comprises an epitope amino acid sequence. 286. The method of claim 284, wherein the peptide induces immune tolerance to cells 287. A method for introducing a nucleic acid into a cell comprising contacting the cell with a lipid particle of any one of claims 1, 4-151, and 162-262. 288. A method for treating a disease or disorder in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of any one of claims 275-280. 289. A method of preventing or delaying the onset or recurrence of a disease or disorder in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of any one of claims 275-280. 290. A method for restoring immune homeostasis in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of any one of claims 275-280. 291. A method for limiting or reducing immunogenicity responses in a subject in need thereof comprising administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition of any one of claims 275-280. 292. The method of any one of claims 288-291, wherein the subject, after the administration to a subject in need thereof, the subject exhibits one or more of: (i) an increase in Treg cells, (ii) reduction in effector T cells, (iii) reduction in B-cells, (iv) reduction in cytokine production, (v) reduction in activated B cells; (vi) reduction in activated effector T cells; or (vii) any combination thereof. 293. A method for limiting or reducing inflammatory responses in a subject in need thereof comprising administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition of any one of claims 275-280. 294. The method of any one of claims 288-293, wherein the pharmaceutical composition is administered intranasally, intracranially, intrathecally, intradermally, intratracheally, transdermally, intravenously, intraperitoneally, by injection, by infusion, intramuscularly, or subcutaneously. 295. The method of any one of claims 288-293, wherein the pharmaceutical composition is administered intravenously, intraperitoneally, by injection, by infusion, intramuscularly, or subcutaneously to the subject. 296. The method of any one of claims 288-295, wherein the subject is a mammal. 297. The method of claim 296, wherein the mammal is a human. 298. The method of any one of claims 288, wherein the disease is an autoimmune disease. 299. The method of claim 298, wherein the autoimmune disease is selected from the group consisting of autoimmune hepatitis, inflammatory bowel disease (including Crohn's disease and ulcerative colitis), nonalcoholic fatty pancreas disease, scleroderma, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, celiac disease, Type 1 diabetes, Guillain- Barré syndrome, Hashimoto's thyroiditis, polymyalgia rheumatic, alopecia areata, fibrosis, psoriasis, pemphigus vulgaris, vitiligo, ankylosing spondylitis, juvenile idiopathic arthritis, psoriatic arthritis, mixed connective tissue disease, neuromyelitis optica, latent autoimmune diabetes in adults (“LADA”), autoimmune thyroid disease, Grave's disease, Addison's disease, autoimmune atrophic gastritis, pernicious anemia, atopic dermatitis, bullous pemphigoid, myasthenia gravis, poly/dermatomyositis), rheumatic fever, primary sclerosing cholangitis, autoimmune uveitis and Behcet's disease), diseases that affect the blood or bone marrow (e.g., autoimmune haemolytic anemia, idiopathic thrombocylopenic purpura, idiopathic leucopenia, Goodpasture's syndrome, autoimmune nephritis, glomerulonephritis, Wegener's granulomatosis, chronic inflammatory demyelinating polyradiculoneuropathy, Sjogren's syndrome, primary biliary cholangitis, Parkinson’s disorder, and antiphospholipid syndrome. 300. The method of claim 299, wherein the autoimmune disease is autoimmune hepatitis, Type 1 diabetes or multiple sclerosis. 301. The method of claim 288, wherein the disease is an infectious disease. 302. The method of claim 288, wherein the disease is a cancer.

Description

LIPID PARTICLES FOR DELIVERING A PAYLOAD CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority benefit under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application Nos.63/619,395 filed January 10, 2024 and 63/511,130 filed June 29, 2023, the disclosure of which is each incorporated herein by reference in its entirety. FIELD OF THE INVENTION [0002] The disclosure relates to lipid particles, pharmaceutical compositions comprising the lipid particles described herein, and methods of use comprising administering the lipid particles described herein. BACKGROUND [0003] Although lipid nanoparticles have been developed to deliver a payload to cells, there remains a need in the art for improved lipid particle compositions that are suitable for therapeutic use. Disclosed herein are lipid particles designed to deliver a payload (e.g., a nucleic acid) that are well-tolerated and provide an adequate therapeutic response. SUMMARY OF THE INVENTION [0004] The present disclosure is based, in part, on lipid particles comprising one or more ionizable lipids, one or more neutral lipids, one or more sterols, one or more charged lipids, and one or more stealth lipids. [0005] Lipid particles comprising cholesteryl hemisuccinate (“CHEMS”) and a payload and optionally one or more of: a. one or more ionizable lipids; b. one or more neutral lipids; c. one or more sterols; and d. one or more stealth lipids are contemplated herein. [0006] Methods of targeting a payload to a spleen of a subject in vivo comprising combining a lipid particle or a composition comprising the payload encapsulated within a lipid particle or a composition comprising CHEMS in a molar amount of at least 11% are also contemplated herein. In some aspects, the lipid particle or composition further comprises one or more ionizable lipids, one or more neutral lipids, one or more sterols, one or more stealth lipids, or any combination thereof. In some aspects, the lipid particle delivers the payload to the spleen. [0007] In some aspects, the one or more ionizable lipids in the lipid particles described herein are one or more selected from the group consisting of DLin-MC3-DMA (“MC3”), DLin-KC2- DMA (“KC2”), ssPalmO-Phe (“SS-OP”), C12-200, SM-102, α-D-tocopherolsuccinoyl (“SS- EC”), ALC-0315 (“ALC”), Tri-N-tridecyl 3-(ethyl(methyl)amino)propanoate (“304-O13”), tetrakis(2-(octyldisulfaneyl)ethyl) 3,3',3'',3'''-(((methylazanediyl)bis(propane-3,1- diyl))bis(azanetriyl))tetrapropionate (“306-O12B”), 9-[4-(dimethylamino)-1-oxobutoxy]- heptadecanedioic acid, 1,17-di-(2Z)-2-nonen-1-yl ester (“L319”), 9,12-octadecadienoic acid, (9Z,12Z)-1,1′,1′′,1′′′-[(3,6-dioxo-2,5-piperazinediyl)bis(4,1-butanediylnitrilodi-4,1-butanediyl)] ester (“OF-C4-Deg-Lin”), 2-(dioctylamino)ethyl nonyl hydrogen phosphate (“9A1P9”), 5-(((3- (dibutylamino)propyl)amino)methyl)-6-hydroxyundecane-1,11-diyl (9Z,9'Z,12Z,12'Z)- bis(octadeca-9,12-dienoate) (“IR-117-17”), 9Z,12Z-octadecadienoic acid, 3-[4,4-bis(octyloxy)-1- oxobutoxy]-2-[[[[3-(diethylamino)propoxy]carbonyl]oxy]methyl]propyl ester (“LP-01”) and 4A3-SC8. In some aspects, the one or more ionizable lipids in the lipid particles described herein are one or more selected from the group consisting of DLin-MC3-DMA (“MC3”), DLin-KC2- DMA (“KC2”), ssPalmO-Phe (“SS-OP”), C12-200, SM-102, α-D-tocopherolsuccinoyl (“SS- EC”), and ALC-0315 (“ALC”). In some aspects, only one ionizable lipid (e.g., SS-OP) is in the lipid particle. [0008] In some aspects, the lipid particles described herein comprises one or more neutral lipids. In some aspects, the one or more neutral lipids in the lipid particle are in a molar amount of at least 0.5%. In some aspects, the one or more neutral lipids in the lipid particles are one or more phosphatidylcholine (“PC”), phosphatidylethanolamine (“PE”), and combination thereof. In some aspects, the one or more neutral lipids in the lipid particles described herein are one or more selected from the group consisting of 1,2-diastearoyl-sn-glycero-3-phosphocholine ("DSPC"), 1,2-dioleoyl-sn-glycero-3-phosphocholine (“DOPC”), 1,2- dioctadecanoyl-sn-glycerol (“DSDG”), 1-2-dioleoyl-sn-glycerol, 1-2-di-(9Z-octadecenoyl)-sn-glycerol ("DODG"), 1,2- dioleoyl-sn-glycero-3-phosphoethanolamine ("DOPE"), diacylphosphatidylcholine, diacylphosphatidylethanolamine, ceramide, sphingomyelin, cephalin, cerebrosides, diacylglycerols dipalmitoylphosphatidylcholine (“DPPC”), palmitoyloleoyl-phosphatidylcholine (“POPC”), palmitoyloleoyl-phosphatidylethanolamine (“POPE”), palmitoyloleyol- phosphatidylglycerol (POPG), dipalmitoyl-phosphatidylethanolamine (“DPPE”), dimyristoyl- phosphatidylethanolamine (“DMPE”), distearoyl-phosphatidylethanolamine (“DSPE”), monomethyl-phosphatidylethanolamine, dimethyl-phosphatidylethanolamine, dielaidoyl- phosphatidylethanolamine (“DEPE”), stearoyloleoyl-phosphatidylethanolamine (“SOPE”), and egg phosphatidylcholine (“EPC”). In some aspects, only one neutral lipid (e.g., DOPE, DODG) is in the lipid