Insightsfrom Computational Studies of Polymeric Systemsfor Nucleic Acid Delivery

The safe and efficient delivery of nucleic acids into cells is a critical step in the success of gene and cell therapies. Although viral vectors are the predominant tools in current gene and cell therapy practices, they present significant challenges including high costs and safety concerns. Nonviral delivery systems for nucleic acids show immense potential for future medicine, particularly as nucleic acid therapeutics continue to be developed for the treatment of a wide range of diseases, including cancer. Significant research efforts, both experimental and computational, have been devoted to the development, characterization, and understanding of nonviral delivery processes. While numerous reviews have documented these research advancements, few have specifically addressed the contributions from computational studies. In this review, we provide an overview of the insights gained from computational and theoretical studies of polymeric systems for nucleic acid delivery. We also highlight future directions where computational and experimental approaches could synergize to advance the field.