ABSTRACT
Successful gene therapy is largely dependent on the development of a vector that has a high transfection efficiency (TE) and as low a cytotoxicity as possible. Viral vectors include recombinant retroviruses, adenoviruses, and adeno-associated viruses that have demonstrated high TE but whose effectiveness is limited due to adverse effects such as immunogenicity and mutagenesis to generate infectious wild-type viruses.1 Synthetic nonviral gene carriers, cationic polymers or liposomes, have elicited much attention as alternatives for viral systems.1-5 They can form soluble complexes with plasmid DNA or antisense oligonucleotide, which can then be carried into cellular
compartments. With suitable design of synthetic gene carriers, it has become possible to construct highly efficient and targetable nonviral systems. However, backbone linkages of most current gene carriers are composed of amide or carbon-carbon bonds, which hardly spontaneously degrade in aqueous solution. For this reason, the potential for current nonbiodegradable gene carriers to accumulate in an endosomal compartment or cell nucleus and adversely interact with the host gene always exists. These issues present a problem with regard to their use in the gene therapy treatment of human disease.
