Use of in vivo phage display to engineer novel adenoviruses for targeted delivery to the cardiac vasculature.
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.
Nicol
Campbell G
CG
British Heart Foundation Glasgow Cardiovascular Research Centre, Glasgow, UK.
Denby
Laura
L
Lopez-Franco
Oscar
O
Masson
Rachel
R
Halliday
Crawford A
CA
Nicklin
Stuart A
SA
Kritz
Angelika
A
Work
Lorraine M
LM
Baker
Andrew H
AH
D000256:Adenoviridae / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002318:Cardiovascular Diseases / Q000503:physiopathology / Q000628:therapy; D003331:Coronary Vessels / Q000378:metabolism* / Q000821:virology*; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000821:virology; D015870:Gene Expression; D005818:Genetic Engineering / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000235:genetics; D019151:Peptide Library; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D017931:DNA Primers; D009842:Oligopeptides; D019151:Peptide Library