RRC ID 38436
Author Jang JH, Koerber JT, Kim JS, Asuri P, Vazin T, Bartel M, Keung A, Kwon I, Park KI, Schaffer DV.
Title An evolved adeno-associated viral variant enhances gene delivery and gene targeting in neural stem cells.
Journal Mol Ther
Abstract Gene delivery to, and gene targeting in, stem cells would be a highly enabling technology for basic science and biomedical application. Adeno-associated viral (AAV) vectors have demonstrated the capacity for efficient delivery to numerous cells, but their application to stem cells has been limited by low transduction efficiency. Due to their considerable advantages, however, engineering AAV delivery systems to enhance gene delivery to stem cells may have an impact in stem cell biology and therapy. Therefore, using several diverse AAV capsid libraries-including randomly mutagenized, DNA shuffled, and random peptide insertion variants-we applied directed evolution to create a "designer" AAV vector with enhanced delivery efficiency for neural stem cells (NSCs). A novel AAV variant, carrying an insertion of a selected peptide sequence on the surface of the threefold spike within the heparin-binding site, emerged from this evolution. Importantly, this evolved AAV variant mediated efficient gene delivery to rat, mouse, and human NSCs, as well as efficient gene targeting within adult NSCs, and it is thus promising for applications ranging from basic stem cell biology to clinical translation.
Volume 19(4)
Pages 667-75
Published 2011-4-1
DOI 10.1038/mt.2010.287
PII S1525-0016(16)30422-1
PMID 21224831
PMC PMC3070092
MeSH Animals Cells, Cultured Chromatography Dependovirus / genetics* Female Fluorescent Antibody Technique Gene Transfer Techniques Neural Stem Cells / virology* Polymerase Chain Reaction Rats Rats, Inbred F344
IF 8.986
Times Cited 58
WOS Category BIOTECHNOLOGY & APPLIED MICROBIOLOGY MEDICINE, RESEARCH & EXPERIMENTAL GENETICS & HEREDITY
Resource
Human and Animal Cells MC3T3-G2/PA6(RCB1127)