In vivo biopanning: A methodological approach to identifying novel targeting ligands for delivery of biological agents to the vasculature.
In order for gene delivery to be clinically acceptable, a number of crucial developments need to be made to existing vectors. Significant advances have been made in the identification of novel platform vectors that possess modified tropism to the native vector, directing infectivity away from nontarget tissues such as the liver. In order to fully optimize these detargeted platform vectors, they need to be retargeted toward a chosen, defined site, which will be defined according to the disease studied. The successful transition of targeting peptides identified using in vitro screening protocols to an in vivo disease model may be compromized by the complexity of delivery into an intact biological system. To this end, peptides identified using in vivo biopanning may prove to be of greater clinical significance given that they were identified in the disease model of choice and so should translate more successfully to the intact preclinical model. Exploitation of the heterogeneity of the vascular endothelium using such an approach will go a long way toward improving the efficiency and achieving site-specific gene expression, with important clinical implications for the systemic application of gene delivery.
Work
Lorraine M
LM
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, UK.
Nicol
Campbell G
CG
Denby
Laura
L
Baker
Andrew H
AH
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001435:Bacteriophages / Q000235:genetics; D001483:Base Sequence; D001808:Blood Vessels / Q000378:metabolism*; D017931:DNA Primers; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D008024:Ligands; D051379:Mice; D016133:Polymerase Chain Reaction
D017931:DNA Primers; D008024:Ligands