Abstract
AbstractThe development of transgenic mouse models that express genes of interest in specific cell types has transformed our understanding of basic biology and disease. However, generating these models is time- and resource-intensive. Here we describe a model system, SELective Expression and Controlled Transduction In Vivo (SELECTIV), that enables efficient and specific expression of transgenes by coupling adeno-associated virus (AAV) vectors with Cre-inducible overexpression of the multi-serotype AAV receptor, AAVR. We demonstrate that transgenic AAVR overexpression greatly increases the efficiency of transduction of many diverse cell types, including muscle stem cells, which are normally refractory to AAV transduction. Superior specificity is achieved by combining Cre-mediated AAVR overexpression with whole-body knockout of endogenous Aavr, which is demonstrated in heart cardiomyocytes, liver hepatocytes and cholinergic neurons. The enhanced efficacy and exquisite specificity of SELECTIV has broad utility in development of new mouse model systems and expands the use of AAV for gene delivery in vivo.
Funder
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Burroughs Wellcome Fund
U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke
U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering
BrightFocus Foundation
International Retinal Research Foundation
U.S. Department of Health & Human Services | NIH | National Eye Institute
Department of Veterans Affairs | Office of Academic Affiliations, Department of Veterans Affairs
Research to Prevent Blindness
Stanford ChEM-H IMA Stanford Center for Optic Disc Drusen
U.S. Department of Health & Human Services | NIH | National Institute on Aging
California Institute for Regenerative Medicine
Li Ka Shing Foundation
Milky Way Research Foundation
U.S. Department of Health & Human Services | NIH | National Cancer Institute
Gouvernement du Canada | Canadian Institutes of Health Research
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Molecular Biology,Biochemistry,Biotechnology
Cited by
6 articles.
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