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Use of in vivo phage display to engineer novel adenoviruses for targeted delivery to the cardiac vasculature
Author(s) -
Nicol Campbell G.,
Denby Laura,
Lopez-Franco Oscar,
Masson Rachel,
Halliday Crawford A.,
Nicklin Stuart A.,
Kritz Angelika,
Work Lorraine M.,
Baker Andrew H.
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.05.037
Subject(s) - phage display , in vivo , gene delivery , context (archaeology) , viral vector , peptide library , peptide , biology , genetic enhancement , computational biology , microbiology and biotechnology , gene , recombinant dna , peptide sequence , biochemistry , genetics , paleontology
We performed in vivo phage display in the stroke prone spontaneously hypertensive rat, a cardiovascular disease model, and the normotensive Wistar Kyoto rat to identify cardiac targeting peptides, and then assessed each in the context of viral gene delivery. We identified both common and strain‐selective peptides, potentially indicating ubiquitous markers and those found selectively in dysfunctional microvasculature of the heart. We show the utility of the peptide, DDTRHWG, for targeted gene delivery in human cells and rats in vivo when cloned into the fiber protein of subgroup D adenovirus 19p. This study therefore identifies cardiac targeting peptides by in vivo phage display and the potential of a candidate peptide for vector targeting strategies.