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CN-122005867-A - Use of a substance that increases IRF5 content in a subject in a product of pulmonary fibrosis

CN122005867ACN 122005867 ACN122005867 ACN 122005867ACN-122005867-A

Abstract

The present application relates to the field of biotechnology, in particular to the use of substances that increase IRF5 content in a subject in a product for pulmonary fibrosis, and further to a product for treating, preventing or alleviating pulmonary fibrosis. The use comprises the use of a substance that increases IRF5 content in a subject in the manufacture of a product for treating, preventing or reducing pulmonary fibrosis. The substance for improving the IRF5 content of the subject can regulate and control the functional state of M2 type macrophages, improve the immune microenvironment of the lung and change the fibrosis promotion state into the anti-fibrosis functional state, thereby effectively reducing the occurrence and development of pulmonary fibrosis.

Inventors

  • MENG SHU
  • SONG ZHIMIN
  • CHEN JINGJING
  • FAN JIAYING
  • ZHANG TINGHONG
  • PAN YAO
  • WANG YAOFENG
  • ZHANG YUN

Assignees

  • 广州国家实验室

Dates

Publication Date
20260512
Application Date
20260319

Claims (10)

  1. 1. Use of a substance that increases IRF5 content in a subject in the manufacture of a product for treating, preventing or alleviating pulmonary fibrosis.
  2. 2. Use of a substance that increases IRF5 content in a subject according to claim 1 for the manufacture of a product for treating, preventing or alleviating pulmonary fibrosis, wherein the substance that increases IRF5 content in a subject comprises an IRF5 polypeptide and a nucleic acid encoding IRF 5.
  3. 3. Use of a substance that increases IRF5 content in a subject according to claim 2, for the preparation of a product for the treatment, prevention or alleviation of pulmonary fibrosis, characterized in that the nucleic acid encoding IRF5 comprises mRNA encoding IRF 5.
  4. 4. Use of a substance that increases IRF5 content in a subject according to claim 3 for the preparation of a product for the treatment, prevention or alleviation of pulmonary fibrosis, characterized in that the nucleotide sequence of the mRNA encoding IRF5 comprises a sequence as shown in SEQ ID No.1 or comprises a sequence having at least 70% identity to the sequence shown in SEQ ID No. 1.
  5. 5. Use of a substance that increases IRF5 content in a subject according to claim 3 for the manufacture of a product for treating, preventing or alleviating pulmonary fibrosis, wherein the mRNA encoding IRF5 further corresponds to at least one of (a) - (d): (a) The 5' end of the mRNA for encoding IRF5 is provided with a cap structure; (b) The 3' end of the mRNA encoding IRF5 has a poly (A) tail; (c) At least one nucleotide in the mRNA encoding IRF5 is a modified nucleotide, and (D) The mRNA encoding IRF5 also contains at least one of a 5'utr and a 3' utr; optionally, the mRNA encoding IRF5 contains at least one modified nucleotide of at least one of 5-methyluridine, 5-methoxyuridine, 2-thiouridine, pseudouridine, N1-methylpseudouridine, 5-methylcytidine, and N6-methyladenosine; Alternatively, the nucleotide sequence of the mRNA encoding IRF5 comprises the sequence shown as SEQ ID NO.1, and the uridine of the mRNA is 5-methyluridine.
  6. 6. Use of a substance for increasing IRF5 content in a subject according to any one of claims 1 to 5 in the manufacture of a product for treating, preventing or alleviating pulmonary fibrosis, wherein the product for treating, preventing or alleviating pulmonary fibrosis further comprises a delivery vehicle; Optionally, the delivery vehicle comprises at least one of a lipid nanoparticle, a liposome, a cationic lipid, a cationic polymer, a metal nano-polymer, a nanorod, a micelle, a microbubble, a cell penetrating peptide, a viral particle, a protein shell, and a lipid sphere.
  7. 7. Use of a substance that increases IRF5 content in a subject according to claim 6 for the manufacture of a product for treating, preventing or alleviating pulmonary fibrosis, wherein said delivery vehicle is selected from delivery vehicles targeting M2 macrophages; Alternatively, the M2 macrophage-targeted delivery vehicle comprises mannose-modified lipid nanoparticles.
  8. 8. Use of a substance that increases IRF5 content in a subject according to claim 7 for the manufacture of a product for the treatment, prevention or alleviation of pulmonary fibrosis, characterized in that the lipid component of the lipid nanoparticle comprises an ionizable lipid, a phospholipid, a structural lipid and a lipid-polyethylene glycol-mannose conjugate; optionally, the mannose-modified lipid nanoparticle satisfies one or more of the following conditions: the ionizable lipid comprises at least one of DLin-MC3-DMA, SM-102, and ALC-0315; the phospholipid comprises at least one of DOPE, DSPC, DLPC, DMPC, DOPC, DPPC, DUPC, POPC, DOPG, DPPG, DPPE, DMPE, DSPE and DOTAP; the structural lipid comprises at least one of cholesterol, fecal sterol, sitosterol, ergosterol, campesterol, stigmasterol, brassicasterol and alpha-tocopherol; The lipid in the lipid-polyethylene glycol-mannose conjugate comprises at least one of DSPE, DMG, ceramide and DMPE; alternatively, the lipid component comprises DLin-MC3-DMA, cholesterol, DOPE, and DSPE-PEG 2000-mannose.
  9. 9. Use of a substance for increasing IRF5 content in a subject according to any of claims 1 to 5 in the manufacture of a product for treating, preventing or alleviating pulmonary fibrosis, wherein the dosage form of the product for treating, preventing or alleviating pulmonary fibrosis comprises a dosage form suitable for pulmonary administration; Alternatively, the dosage forms suitable for pulmonary administration include aerosols, dry powder inhalants, liquid formulations for aerosol inhalation and soft mist inhalants.
  10. 10. A product for the treatment, prevention or alleviation of pulmonary fibrosis, characterized in that the product for the treatment, prevention or alleviation of pulmonary fibrosis comprises a substance which increases IRF5 content in a subject as defined in any one of the claims 1-9, and a delivery vehicle which targets M2 macrophages as defined in claim 7 or 8.

Description

Use of a substance that increases IRF5 content in a subject in a product of pulmonary fibrosis Technical Field The present application relates to the field of biotechnology, in particular to the use of substances that increase IRF5 content in a subject in a product for pulmonary fibrosis, and further to a product for treating, preventing or alleviating pulmonary fibrosis. Background Pulmonary fibrosis is a type of fatal disease characterized by progressive fibrotic remodeling of the pulmonary stroma, which is typically represented by idiopathic pulmonary fibrosis (Idiopathic Pulmonary Fibrosis, IPF). The existing medicines mainly play a role by inhibiting fibroblast activation or collagen deposition, but have limited curative effects and can not effectively reverse the disease process. At present, medicines for treating pulmonary fibrosis mainly comprise two types of anti-fibrosis medicines, namely pirfenidone (Pirfenidone) and nidanib (Nintedanib), and the two anti-fibrosis medicines can delay the decline speed of the pulmonary function to a certain extent by inhibiting mechanisms such as fibroblast proliferation, extracellular matrix deposition reduction, fibrosis signal channel blocking and the like. However, pirfenidone and nilamide have the defects that the existing medicines only can slow down the disease progression, but cannot prevent or reverse the formed pulmonary fibrosis, the pirfenidone and the nilamide have serious side effects, the pirfenidone is common in photosensitive rash, gastrointestinal tract reaction and potential hepatotoxicity, and the nilamide is most prominent in diarrhea, and is often accompanied by appetite reduction, weight reduction and liver enzyme elevation. Therefore, more therapeutic targets related to the pulmonary fibrosis are discovered to develop new products for treating, preventing or relieving the pulmonary fibrosis, and the products have important scientific value and clinical urgency for filling the currently clinical unmet therapeutic demands and breaking through the curative effect bottleneck of the existing anti-fibrosis drugs. Disclosure of Invention Based on this, it is necessary to provide a use of a substance that increases IRF5 content in a subject in a product of pulmonary fibrosis. In a first aspect, there is provided the use of a substance that increases IRF5 content in a subject in the manufacture of a product for treating, preventing or alleviating pulmonary fibrosis. In alternative embodiments, the agent that increases IRF5 content in a subject comprises an IRF5 polypeptide and a nucleic acid encoding IRF 5. In alternative embodiments, the nucleic acid encoding IRF5 comprises mRNA encoding IRF 5. In alternative embodiments, the nucleotide sequence of the mRNA encoding IRF5 comprises a sequence as set forth in SEQ ID No.1, or comprises a sequence having at least 70% identity to the sequence set forth in SEQ ID No. 1. In an alternative embodiment, the mRNA encoding IRF5 further corresponds to at least one of (a) - (d): (a) The 5' end of the mRNA for encoding IRF5 is provided with a cap structure; (b) The 3' end of the mRNA encoding IRF5 has a poly (A) tail; (c) At least one nucleotide in the mRNA encoding IRF5 is a modified nucleotide, and (D) The mRNA encoding IRF5 also contains at least one of a 5'utr and a 3' utr. In an alternative embodiment, the mRNA encoding IRF5 contains at least one modified nucleotide of at least one of 5-methyluridine, 5-methoxyuridine, 2-thiouridine, pseudouridine, N1-methylpseudouridine, 5-methylcytidine, and N6-methyladenosine. In an alternative embodiment, the nucleotide sequence of the mRNA encoding IRF5 comprises the sequence shown as SEQ ID NO.1, and the uridine of the mRNA is 5-methyluridine. In alternative embodiments, the product for treating, preventing or reducing pulmonary fibrosis further comprises a delivery vehicle. In alternative embodiments, the delivery vehicle comprises at least one of a lipid nanoparticle, a liposome, a cationic lipid, a cationic polymer, a metal nano-polymer, a nanorod, a micelle, a microbubble, a cell penetrating peptide, a viral particle, a protein shell, and a lipid sphere. In alternative embodiments, the delivery vehicle is selected from delivery vehicles targeting M2 macrophages. In alternative embodiments, the M2 macrophage-targeted delivery vehicle comprises mannose-modified lipid nanoparticles. In alternative embodiments, the lipid component of the lipid nanoparticle comprises an ionizable lipid, a phospholipid, a structural lipid, and a lipid-polyethylene glycol-mannose conjugate; In alternative embodiments, the mannose-modified lipid nanoparticle satisfies one or more of the following conditions: the ionizable lipid comprises at least one of DLin-MC3-DMA, SM-102, and ALC-0315; the phospholipid comprises at least one of DOPE, DSPC, DLPC, DMPC, DOPC, DPPC, DUPC, POPC, DOPG, DPPG, DPPE, DMPE, DSPE and DOTAP; the structural lipid comprises at least one of cholesterol, fecal sterol,