ABSTRACT
The safe and efficient delivery of therapeutic DNA to cells represents a fundamental obstacle to the clinical success of gene therapy. Cationic polymers have been investigated broadly as nonviral gene delivery agents because they can spontaneously self-assemble with and condense plasmid DNA (pDNA) into structures small enough to enter cells via endocytosis.1 Many different cationic polymers are effective at overcoming these early entry-based barriers to gene delivery. The incorporation of additional functionality into polycationic scaffolds has yielded more sophisticated polymers that further protect DNA and help surmount other important intracellular barriers to efficient delivery and expression.2-4 Despite recent advances, however, conventional polymeric vectors such as polyethylenimine (PEI)5,6 have been associated with substantial cytotoxicity and polycations remain far less effective at mediating gene transfer than viral vectors.7 The efficiency and general safety of synthetic cationic polymers — and an understanding of the structure-property relationships that define and influence them — must ultimately be addressed to support the continued advance of these materials into the clinic.
