title: Acquisition of selective antitumoral effects of recombinant adeno-associated virus by genetically inserting tumor-targeting peptides into capsid proteins.
abstract: Recombinant adeno-associated virus serotype 5 (rAAV5) is considered to be a promising gene transfer vehicle. However, preferential gene delivery to the tumor remains a requirement for cancer treatment. We generated rAAV5 mutants bearing tumor marker-binding peptides and analyzed their properties as viral vectors, as well as their transduction efficiencies and preferential antitumoral potencies. All of the mutants were successfully produced. Transduction analyses showed that rAAV5 mutants harboring tumor-homing peptides, including RGD and TnC, transduced human cancer cells expressing corresponding receptors on their surfaces. RGDS peptides and TnC antibodies significantly suppressed transduction by rAAV5-RGD and rAAV5-TnC. Cytotoxicity was evident upon transfer of HSV-TK to cells by re-targeted rAAV5. These results provide evidence that rAAV5 vectors, genetically armed with tumor-targeting ligands, preferentially infect human cancer cells harboring the corresponding receptors, thereby inducing antitumoral effects. Further optimization of rAAV5 mutant viruses should thus facilitate practical exploitation of these vectors for gene-based cancer treatment.
authors: Department of Microbiology, University of Ulsan College of Medicine, Seoul.
authors: Han Saem
authors: HS
authors: Lee
authors: Ji Yun
authors: JY
authors: Kim
authors: Won Il
authors: WI
authors: Lee
authors: Sung Jin
authors: SJ
authors: Kim
authors: Min Ji
authors: MJ
authors: Ko
authors: Sunjoo
authors: S
authors: Jeong
authors: Keerang
authors: K
authors: Park
authors: Han
authors: H
authors: Choe
authors: Heuiran
authors: H
authors: Lee