Quinine-Based Polymers Are Versatile and Effective Vehicles for Intracellular pDNA, mRNA, and Cas9 Protein Delivery

Quinine-based polymers have previously demonstrated promising performance in delivering pDNA in cells owing to their electrostatic as well as the nonelectrostatic interactions with pDNA. Herein, we evaluate whether quinine-based polymers are versatile for delivery of mRNA and Cas9-sgRNA complexes, especially in a serum-rich environment. Both mRNA and the Cas9-sgRNA complex are potent therapeutics that are structurally, chemically, and functionally very different from pDNA. By exploring a family of 7 quinine-based polymers that vary in monomer structure and polymer composition, we tested numerous formulations (42 with pDNA, 96 with mRNA, and 48 with Cas9-sgRNA) for payload-polymer complexation and delivery to compare payload-dependent structure-activity relationships. Several formulations demonstrated performance comparable to or better than the commercially available transfection agent jetPEI. The results of this study demonstrate the potential of quinine-based as a versatile carrier platform for delivering a wide range of nucleic acid therapeutics and serving the drug delivery needs in the field genetic medicine.