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.

Multifunctional nucleic acid nanostructures for gene therapies

Nucleic acid nanotechnology has been developed to be a promising strategy to construct various nano-biomaterials with structural programmability, spatial addressability, and excellent biocompatibility. Self-assembled nucleic acid nanostructures have been employed in a variety of biomedical applications, such as bio-imaging, diagnosis, and therapeutics. In this manuscript, we will review recent progress in the development of multifunctional nucleic acid nanostructures as gene drug delivery vehicles. Therapeutic systems based on RNA interference （RNAi）, clustered regularly interspaced short palindromic repeat associated proteins 9 system （CRISPR/Cas9） genome editing, gene expression, and CpG-based immunostimulation will be highlighted. We will also discuss the challenges and future directions of nucleic acid nanotechnology in biomedical research.

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.

Nucleic acid-based aggregates and their biomedical applications

The more than three decades of research in nucleic acid nanotechnology has led to the thrilling progress in rationally designed structures and artificial molecular devices with programmable functions and various applications.Nucleic acid–based aggregates feature precise molecular recognition and sequence programmability,versatility,as well as marked biocompatibility,providing promising candidates for biomedical applications.In this minireview,we summarize the recent,successful efforts to construct and employ nucleic acid–based aggregates for biomedical applications,including drug delivery,bioimaging,biosensing,cell analysis,and combined cancer therapy.We also discuss the remaining challenges and opportunities in the field.