title: Integration of adeno-associated virus-derived peptides into nonviral vectors to synergistically enhance cellular transfection.
abstract: This study describes a simple, versatile approach for developing a nonviral gene carrier by adopting the highly efficient gene delivery properties of the adeno-associated virus (AAV). Specific viral peptides (r3.45_hepBD) extracted from AAV r3.45, which directly evolved to improve gene delivery capabilities in many cell types, were conjugated onto branched polyethylenimine (PEI) to form hybrid gene carriers. AAV r3.45 carries a sequence insertion (LATQVGQKTA; r3.45) within the heparin-binding domain (LQRGNRQA; hepBD), which ultimately comprises a novel sequence (LQRGNLATQVGQKTARQA; r3.45_hepBD) on the capsid. This sequence is hypothesized to be a crucial cue to enhance gene delivery efficiency. Consequently, the intimate interactions of the conjugated r3.45_hepBD with the glycosaminoglycans, including chondroitin sulfate, resulted in significantly enhanced cellular transfection of DNA/PEI-r3.45_hepBD complexes. The successful establishment of a nonviral system that is built with novel peptides will provide a powerful means for developing a substantial number of gene therapy applications.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, Korea, 120-749.
authors.forename: Jung-Suk
authors.initials: JS
authors.lastname: Kim
authors.forename: Eunmi
authors.initials: E
authors.lastname: Kim
authors.forename: Ji-Seon
authors.initials: JS
authors.lastname: Oh
authors.forename: Jae-Hyung
authors.initials: JH
authors.lastname: Jang
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D000229:Dependovirus; D004705:Endocytosis; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D014161:Transduction, Genetic; D014162:Transfection / Q000379:methods*; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D014764:Viral Proteins