Bio & Medicine

The researchers created genetically encoded DNA origami for in vivo targeted and precise gene therapy.

Nucleic acid molecules have been developed as gene therapeutic drugs because they can carry genetic information. Nucleic acid is able to precisely self-assemble into nanostructures of specific sizes and shapes by using complementary base pairing to encode functional genes. However, gene therapy has rarely utilized these DNA nanostructures’ inherent properties (encoding genes).

Ding Baoquan’s team at the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences (CAS) created a genetically encoded DNA origami for precise and targeted gene therapy in vivo in a study that was published in the Journal of the American Chemical Society.

“Efficient self-assembly and chemical modification of nucleic acid are the foundation of the genetically encoded DNA origami’s key design,”

 Wu Xiaohui from NCNST, first author of the paper.

“The critical plan of the hereditarily encoded DNA origami depends on productive self-get-together and synthetic adjustment of nucleic acids,” said Wu Xiaohui from NCNST, the first creator of the paper.

By connecting their respective staple strands, the complementary sense and antisense strands of a gene can be folded directly into two DNA origami monomers. The researchers then constructed genetically encoded DNA origami with precisely organized lipids on the surface for in-situ lipid growth following hybridization.

Antitumor gene (p53)-encoded and lipid-coated DNA origami can induce a significant upregulation of the p53 protein in tumor cells following decoration with the tumor-targeting group for effective in vivo tumor therapy.

Ding from NCNST, one of the corresponding authors of the paper, stated, “The genes folded and delivered by this method are not limited in length as viral vectors, and due to the presence of DNA origami templates, there are more options for lipid components without being restricted by the composition and concentration formula of traditional liposomes.”

More information: Xiaohui Wu et al, Genetically Encoded DNA Origami for Gene Therapy In Vivo, Journal of the American Chemical Society (2023). DOI: 10.1021/jacs.3c02756

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