| Apr 25, 2023 |
Gene-encoded DNA origami for precise In vivo gene therapy
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(Nanowerk News) As carriers of genetic information, nucleic acid molecules have emerged as promising candidates for gene-based therapeutic interventions. Nucleic acids, through the principle of complementary base pairing, can not only encode functional genes but can also accurately self-assemble into nanostructures with predetermined dimensions and morphologies. However, the inherent property (gene encoding) of these DNA nanostructures has been infrequently utilized in gene therapy applications.
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In a research article published in the Journal of the American Chemical Society ("Genetically Encoded DNA Origami for Gene Therapy In Vivo"), Baoquan Ding's team from the National Center for Nanoscience and Technology (NCNST) at the Chinese Academy of Sciences (CAS) has designed a gene-encoded DNA origami for targeted and precise in vivo gene therapy.
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"The fundamental design of the gene-encoded DNA origami relies on the efficient self-assembly and chemical modification of nucleic acids," explained Xiaohui Wu from NCNST, the study's lead author.
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The complementary sense and antisense strands of a gene can be directly folded into two DNA origami monomers using their corresponding staple strands. By hybridizing these monomers, the scientists constructed gene-encoded DNA origami that featured meticulously arranged lipids on the surface to facilitate in situ lipid growth.
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Following the addition of a tumor-targeting moiety, the resulting lipid-coated DNA origami encoded with the antitumor gene (p53) was found to induce a significant upregulation of the p53 protein in tumor cells, thereby leading to effective in vivo tumor therapy.
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"The genes folded and delivered through this approach are not restricted by length, as is the case with viral vectors. Furthermore, the presence of DNA origami templates allows for a wider range of lipid components, without being constrained by the composition and concentration requirements of conventional liposomes," noted Ding from NCNST, a corresponding author of the publication.
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