Development of renal-targeted vectors through combined in vivo phage display and capsid engineering of adenoviral fibers from serotype 19p.

Development of renal-targeted vectors through combined in vivo phage display and capsid engineering of adenoviral fibers from serotype 19p. Research Abstract Details 

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Development of renal-targeted vectors through combined in vivo phage display and capsid engineering of adenoviral fibers from serotype 19p. Abstract Text:

Laura Denby,Lorraine M Work,Dan J Von Seggern,Eugene Wu,John H McVey,Stuart A Nicklin,Andrew H Baker,

The potential efficacy of gene delivery is dictated by the infectivity profile of existing vectors, which is often restrictive. In order to target cells and organs for which no efficient vector is currently available, a promising approach would be to engineer vectors with novel transduction profiles. Applications that involve injecting adenovirus (Ad) vectors into the bloodstream require that native tropism for the liver be removed, and that targeting moieties be engineered into the capsid. We previously reported that pseudotyping the Ad serotype 5 fiber for that of Ad19p results in reduced hepatic transduction. In this study we show that this may be caused, at least in part, by a reduction in the capacity of the Ad19p-based virus to bind blood coagulation factors. It is therefore a potential candidate for vector retargeting, focusing on the kidney as a therapeutic target. We used in vivo phage display in rats, and identified peptides HTTHREP and HITSLLS that homed to the kidneys following intravenous injection. We engineered the HI loop of Ad19p to accommodate peptide insertions and clones. Intravenous delivery of each peptide-modified virus resulted in selective renal targeting, with HTTHREP and HITSLLS-targeted viruses selectively transducing tubular epithelium and glomeruli, respectively. Our study has important implications for the use of genetic engineering of Ad fibers to produce targeted gene delivery vectors.

Development of renal-targeted vectors through combined in vivo phage display and capsid engineering of adenoviral fibers from serotype 19p. Publishing Authors By Initials

L Denby,LM Work,DJ Seggern,E Wu,JH McVey,SA Nicklin,AH Baker,

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Development of renal-targeted vectors through combined in vivo phage display and capsid engineering of adenoviral fibers from serotype 19p. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular therapy : the journal of the American So

VOLUME: 15

Page Numbers: 1647-54

Journal Abbreviation: Mol. Ther.

ISSN: 1525-0016

DAY: 5

MONTH: 06

YEAR: 2007

Development of renal-targeted vectors through combined in vivo phage display and capsid engineering of adenoviral fibers from serotype 19p. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Development of renal-targeted vectors through combined in vivo phage display and capsid engineering of adenoviral fibers from serotype 19p.

AFFILIATION: British Heart Foundation Glasgow, Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.

Country: United States

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MEDLINETA: Mol Ther

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