Long and Covalently Conjugated Branched DNA Structures for in Situ Gelation in Vivo

DNA nanotechnology has been widely employed for biomedical applications.However,most DNA nanomaterials rely on noncovalent complementary base pairing of short single-stranded DNA oligonucleotides.Herein,we describe a general strategy to construct a long and covalently conjugated branched DNA structure for fast and in situ gelation in vivo.In our design,a short and covalently conjugated branched DNA structure can normally be employed as the DNA primer in the terminal deoxynucleotidyl transferase-dependent enzymatic polymerization system.After enzymatic extension,the DNA aptamer-modified branched DNA structures with the sequences of poly T or poly A can immediately coassemble for in situ encapsulation of the target protein and tumor cell.The fast and in situ gelation system can function in a murine model of local tumor recurrence for targeting residual tumor cells to achieve long-term drug release for efficient tumor inhibition in vivo.This rationally developed DNA self-assembly strategy provides a new avenue for the development of multifunctional DNA nanomaterials.

Chemically modified DNA nanostructures for drug delivery

Based on predictable,complementary base pairing,DNA can be artificially pre-designed into versatile DNA nanostructures of well-defined shapes and sizes.With excellent addressability and biocompatibility,DNA nanostructures have been widely employed in biomedical research,such as biosensing,bio-imaging,and drug delivery.With the development of the chemical biology of nucleic acid.