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

doi:10.1038/mt.2010.287

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

Department of Chemical and Biomolecular Engineering

Research output: Contribution to journal › Article › peer-review

78 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 language	English
Pages (from-to)	667-675
Number of pages	9
Journal	Molecular Therapy
Volume	19
Issue number	4
DOIs	https://doi.org/10.1038/mt.2010.287
Publication status	Published - 2011 Apr

Bibliographical note

Funding Information:
This work was supported by California Institute for Regenerative Medicine Training grant number T1-00007 and grant number RT1-01021, and by National Research Foundation (NRF) grant funded by the Korea government (MEST) through the Active Polymer Center for Pattern Integration (No. R11-2007-050-00000-0). KIP was supported by Stem Cell Research Center grant and Healthcare Technology R&D Project grant funded by Korean Government. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of CIRM or any other agency of the State of California. The authors are also grateful to Prof Andrew Wurmser for kindly providing murine NSCs and Ilsun Kim for technical support on human NSC culture.

All Science Journal Classification (ASJC) codes

Molecular Medicine
Molecular Biology
Genetics
Pharmacology
Drug Discovery

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10.1038/mt.2010.287

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

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.",

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

note = "Funding Information: This work was supported by California Institute for Regenerative Medicine Training grant number T1-00007 and grant number RT1-01021, and by National Research Foundation (NRF) grant funded by the Korea government (MEST) through the Active Polymer Center for Pattern Integration (No. R11-2007-050-00000-0). KIP was supported by Stem Cell Research Center grant and Healthcare Technology R&D Project grant funded by Korean Government. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of CIRM or any other agency of the State of California. The authors are also grateful to Prof Andrew Wurmser for kindly providing murine NSCs and Ilsun Kim for technical support on human NSC culture.",

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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