Click Nucleic Acid (CNA) Hydrogels for Targeted Drug Delivery

DNA has the unique property of complementary base pairing, making it a desirable material for a variety of applications including aptamer-based drug delivery, regulation of gene transcription, and self-assembly of nanomaterials. However, DNA is readily degraded by nucleases, limiting the use of DNA as a material outside of a controlled laboratory environment. Here, we report the development of a synthetic DNA analogue, Click Nucleic Acid (CNA), which exhibits the same base-pairing properties of DNA but is resistant to nuclease degradation. CNA monomers were synthesized by properly protecting and functionalizing each of the four DNA nucleobases—Adenine, Thymine, Guanine, and Cytosine. These nucleobases were then attached to a thiol and acrylamide functionalized monomer backbone that can be polymerized via the thiol-Michael addition click reaction. In addition, through sequential thiol-Michael additions, sequence-controlled oligomers can be produced on a solid support.