Tissue specific promoters improve specificity of AAV9 mediated transgene expression following intra-vascular gene delivery in neonatal mice

Christina A. Pacak, Yoshihisa Sakai, Bijoy D. Thattaliyath, Cathryn S. Mah, Barry J. Byrne

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77 Scopus citations


The AAV9 capsid displays a high natural affinity for the heart following a single intravenous (IV) administration in both newborn and adult mice. It also results in substantial albeit relatively lower expression levels in many other tissues. To increase the overall safety of this gene delivery method we sought to identify which one of a group of promoters is able to confer the highest level of cardiac specific expression and concurrently, which is able to provide a broad biodistribution of expression across both cardiac and skeletal muscle. The in vivo behavior of five different promoters was compared: CMV, desmin (Des), alpha-myosin heavy chain (α-MHC), myosin light chain 2 (MLC-2) and cardiac troponin C (cTnC). Following IV administration to newborn mice, LacZ expression was measured by enzyme activity assays. Results showed that rAAV2/9-mediated gene delivery using the α-MHC promoter is effective for focal transgene expression in the heart and the Des promoter is highly suitable for achieving gene expression in cardiac and skeletal muscle following systemic vector administration. Importantly, these promoters provide an added layer of control over transgene activity following systemic gene delivery.

Original languageEnglish (US)
Article number13
JournalGenetic Vaccines and Therapy
StatePublished - Sep 23 2008
Externally publishedYes

Bibliographical note

Funding Information:
We would like to express our gratitude to Mark Potter, the University of Florida Powell Gene Therapy Center (PGTC) and Irene Zolotukhin for providing technical expertise in producing the viruses used in this study. We would also like to thank Stacy Porvasnik for assisting with animal work and Dr. Steven Potter (Children's Hospital Medical Center, Cincinnati, Ohio) for providing the immortalized line of cardiomyocytes. This work was supported in part by an American Heart Association Pre-doctoral Fellowship Award-Florida and Puerto Rico Affiliate (to CAP), the NIH National Heart, Lung, and Blood Institute grant PO1 HL59412; National Institute of Diabetes and Digestive and Kidney Diseases grant PO1 DK58327; AT-NHLBI-U01 HL69748; and the AHA National Center (to C.S.M.).


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