Gene-encoded DNA origami for precise In vivo gene therapy


April 25, 2023

(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 also can accurately self-assemble into nanostructures with predetermined dimensions and morphologies. However, this inherent property (gene coding) of DNA nanostructures is seldom used in gene therapy applications.

In a research article published in Journal of the American Chemical Society (“Genetically Coded DNA Origami for In Vivo Gene Therapy”), Baoquan Ding’s team from the National Center for Nanoscience and Technology (NCNST) at the Chinese Academy of Sciences (CAS) have designed gene-encoded DNA origami for targeted and precise in vivo gene therapy.

“The fundamental design of gene-encoded DNA origami relies on efficient self-assembly and chemical modification of nucleic acids,” explains Xiaohui Wu of NCNST, lead author of the study.

The complementary and antisense sense strands of a gene can be directly folded into two DNA origami monomers using the appropriate staple strands. By hybridizing these monomers, scientists construct gene-encoded DNA origami featuring lipids carefully arranged on the surface to facilitate in place lipid growth.

Following addition of tumor targeting sections, the resulting lipid-coated DNA origami encoded with an antitumor gene (p53) was found to induce significant upregulation of p53 protein in tumor cells, leading to an effective life tumor therapy.

“Genes folded and delivered via this approach are not limited by length, as is the case with viral vectors. In addition, the existence of DNA origami templates allows for a wider range of lipid components, without being limited by the compositional and concentration requirements of conventional liposomes,” said Ding of NCNST, corresponding author of the publication.


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