| A Potential Role of Distinctively Delayed Blood Clearance of Recombinant Adeno-associated Virus Serotype 9 in Robust Cardiac Transduction. | |
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MedLine Citation:
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PMID: 21364543 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Recombinant adeno-associated virus serotype 9 (rAAV9) vectors show robust in vivo transduction by a systemic approach. It has been proposed that rAAV9 has enhanced ability to cross the vascular endothelial barriers. However, the scientific basis of systemic administration of rAAV9 and its transduction mechanisms have not been fully established. Here, we show indirect evidence suggesting that capillary walls still remain as a significant barrier to rAAV9 in cardiac transduction but not so in hepatic transduction in mice, and the distinctively delayed blood clearance of rAAV9 plays an important role in overcoming this barrier, contributing to robust cardiac transduction. We find that transvascular transport of rAAV9 in the heart is a capacity-limited slow process and occurs in the absence of caveolin-1, the major component of caveolae that mediate endothelial transcytosis. In addition, a reverse genetic study identifies the outer region of the icosahedral threefold capsid protrusions as a potential culprit for rAAV9's delayed blood clearance. These results support a model in which the delayed blood clearance of rAAV9 sustains the capacity-limited slow transvascular vector transport and plays a role in mediating robust cardiac transduction, and provide important implications in AAV capsid engineering to create new rAAV variants with more desirable properties. |
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Authors:
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Nicole M Kotchey; Kei Adachi; Maliha Zahid; Katsuya Inagaki; Rakshita Charan; Robert S Parker; Hiroyuki Nakai |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-01 |
Journal Detail:
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Title: Molecular therapy : the journal of the American Society of Gene Therapy Volume: - ISSN: 1525-0024 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-2 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100890581 Medline TA: Mol Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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