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 nano materials.