An evolved adeno-associated viral variant enhances gene delivery and gene targeting in neural stem cells

Jae Hyung Jang, James T. Koerber, Jung Suk Kim, Prashanth Asuri, Tandis Vazin, Melissa Bartel, Albert Keung, Inchan Kwon, Kook In Park, David V. Schaffer

Research output: Contribution to journalArticle

63 Citations (Scopus)

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 librariesincluding randomly mutagenized, DNA shuffled, and random peptide insertion variantswe 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.

Original languageEnglish
Pages (from-to)667-675
Number of pages9
JournalMolecular Therapy
Volume19
Issue number4
DOIs
Publication statusPublished - 2011 Apr

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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    Jang, J. H., Koerber, J. T., Kim, J. S., Asuri, P., Vazin, T., Bartel, M., Keung, A., Kwon, I., Park, K. I., & Schaffer, D. V. (2011). An evolved adeno-associated viral variant enhances gene delivery and gene targeting in neural stem cells. Molecular Therapy, 19(4), 667-675. https://doi.org/10.1038/mt.2010.287