JP-2025514316-A5 -

Dates

Publication Date

20260511

Application Date

20230428

Description

The inventors hypothesize that their HS-modified DNA origami shells can function as cell surface decoys, capturing viruses, preventing interaction with the cell surface, and thus reducing the effective viral load in acute infections. Testing the therapeutic potential of this system for reducing viral load in vivo remains an important challenge for the future. Beyond viral neutralization, the inventors' system can also function as a sink for capturing related viral proteins (Figure 20) and other by-products such as subviral particles that may overwhelm the immune system (Zelikin, loc. cit.; Chai, N. et al., J. Virol. 82 (2008) 7812-7817). Overall, the inventors' results strongly suggest that their heparan sulfate-modified shell library has the potential to be a suitable therapeutic platform for combating viral infections. Some aspects of the present invention are described below. 1. A DNA-based nanostructure, The DNA-based nanostructure is a shell having a cavity surrounded by the DNA-based nanostructure, The DNA-based nanostructure is formed from self-assembling DNA-based components, Each of the self-assembling DNA-based components is formed by a single-stranded DNA template strand and a set of oligonucleotides complementary to the single-stranded DNA template. Each of the oligonucleotides is complementary to either one continuous DNA sequence stretch or at least two discontinuous DNA sequence stretches on the single-stranded DNA template. Each of the self-assembling DNA-based components is a triangular prism and/or a rectangular prism, in particular a triangular prism, Each subset of one or more oligonucleotides in one or more of the self-assembling DNA-based components is linked to a construct containing at least one sulfonated or sulfated polysaccharide group toward the interior of the cavity, particularly a construct containing one or two sulfonated or sulfated polysaccharide groups, Each construct comprises (i) a handle having at least one binding site for the sulfonated or sulfated polysaccharide group, and (ii) the sulfonated or sulfated polysaccharide group(s) attached to the handle, wherein the handle has a length corresponding to the length of a single-stranded oligonucleotide containing at least 30 nucleotides. 2. The DNA-based nanostructure according to item 1, wherein each of the handles comprises two binding sites for the sulfonated or sulfated polysaccharide group. 3. The DNA-based nanostructure according to item 1 or 2, wherein each of the sulfonated or sulfated polysaccharide groups is independently selected from the list of heparin, heparan sulfate, hybrid heparan sulfate, carrageenan, cellulose sulfate, and dextrin 2-sulfate. 4. The DNA-based nanostructure according to item 3, wherein each of the sulfonated or sulfated polysaccharides is independently selected from heparan sulfate and hybrid heparan sulfate, in particular heparan sulfate. 5. The DNA-based nanostructure according to any one of items 1 to 4, wherein one or more of the self-assembling DNA-based components in the subset comprises n single-stranded oligonucleotides as handles, each handle independently linked to at least one sulfonated or sulfated polysaccharide group, and n is an integer independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12, in particular n is 9. 6. A DNA-based nanostructure according to any one of items 1 to 5, wherein the handle is a single-stranded oligonucleotide having a length of 30 to 60 nucleotides, particularly 40 to 55 nucleotides, and more specifically 45 to 50 nucleotides. 7. The DNA-based nanostructure according to any one of items 1 to 6, wherein each of the sulfonated or sulfated polysaccharide groups contains an oligonucleotide having a sequence complementary to the oligonucleotide stretch contained in the handle. 8. A DNA-based nanostructure according to any one of items 1 to 7, which is a closed three-dimensional geometric shape, particularly a sphere, a spherical cylinder, and a polyhedron, particularly a tetrahedron, octahedron, or icosahedron, formed in situ from the self-assembling DNA-based components in the presence of the encapsulated virus or viral particles. 9. A DNA-based nanostructure according to any one of items 1 to 7, which is a shell having an opening for accessing the cavity. 10. A DNA-based nanostructure according to any one of items 1 to 7, comprising a combination of first and second subshells, each having an opening for accessing first and second internal cavities, wherein the first and second internal cavities together form the cavity, and in particular the first and second subshells are connected by at least one linker. 11. A DNA-based nanostructure based on an icosahedral structure, as described in any of items 1 to 10. 12. The DNA-based nanostructure according to item 11, wherein the DNA-based nanostructure is formed of self-assembling DNA-based components, each of which is a triangular prism and/or a rectangular parallelepiped, particularly a triangu