Polyvinylamine with moderate binding affinity as a highly effective vehicle for RNA delivery

Polymeric carriers for RNA therapy offer potential advantages in terms of low immunogenicity, promoting modifiability and accelerating intracellular transport. However, balancing high transfection efficacy with low toxicity remains challenging with polymer-based vehicles; indeed, polyethyleneimine (PEI) remains the gold standard polymer for this purpose despite its significant toxicity limitations. Herein, we demonstrate the po-tential of polyvinylamine (PVAm), a commodity high-charge cationic polymer used in the papermaking industry and has similar structure with PEI, as an alternative carrier for RNA delivery. High levels of transfection of normal, tumor, and stem cells with a variety of RNA cargoes including small interfering RNA (siRNA), microRNA (miRNA), and recombinant RNA can be achieved in vitro under the proper complex conditions. While, both the anti-tumor effect achieved in a xenograft osteosarcoma model and lipid-lowering activity observed in a hyper-lipidemia mice indicate the potential for highly effective in vivo activity. Of note, both the transfection efficiency and the cytotoxicity of PVAm compare more favorably with those of PEI, with PVAm offering the additional advantages of simpler purification and significantly lower cost. In addition, the mechanism for the difference in transfection efficiency between PVAm and PEI is explored by molecular docking as well as analyzing the process of association and dissociation between polymers (PVAm and PEI) and nucleic acids. Our research provides a novel, non-toxic, and cost-effective carrier candidate for next generation RNA therapy, and elucidates the po-tential mechanism of PVAm for its efficient delivery of RNA.

Automated summary

Polymeric carriers, such as polyvinylamine (PVAm), offer potential advantages in RNA therapy by balancing high transfection efficacy with low toxicity. PVAm demonstrates high levels of transfection and shows promise for in vivo activity, with advantages over the gold standard polymer, polyethyleneimine (PEI), including simpler purification and lower cost. Mechanism analysis reveals the potential of PVAm for efficient RNA delivery.