Abstract
Gene therapy holds great promise for various medical and biomedical applications. Nonviral gene delivery systems formed by cationic polymer and nucleic acids (e.g., polyplexes) have been extensively investigated for targeted gene therapy; however, their in vitro and in vivo stability is affected by both their intrinsic properties such as chemical compositions (e.g., polymer molecular weight and structure, and N/P ratio) and a number of environmental factors (e.g., shear stress during circulation in the bloodstream, interaction with the serum proteins, and physiological ionic strength). In this review, we surveyed the effects of a number of important intrinsic and environmental factors on the stability of polymeric gene delivery systems, and discussed various strategies to enhance the stability of polymeric gene delivery systems, thereby enabling efficient gene delivery into target cells. Future opportunities and challenges of polymeric nucleic acid delivery nanosystems were also briefly discussed.