Gene therapy holds promise for treatment of a variety of lethal diseases including cancer, cystic fibrosis. Delivery of genes via viruses or synthetic vectors requires that DNA be delivered past host defenses that have evolved to keep foreign DNA from being incorporated and expressed. One of the key modes of defense is provided by deoxyribonucleases (DNases). Development of DNase inhibitors would be expected to enable delivery of a larger fraction of administered DNA, thereby increasing efficacy. In this work, DNase inhibitors will be identified using phage display, a high-throughput screening technology. Quantitative in vitro experiments will elucidate the effect of DNase on the kinetic trafficking dynamics of gene delivery. Quantitative in vivo experiments will be designed based on in vitro results to demonstrate increased levels of transfection with DNase inhibitors.
|Choi, Suk-Jung; Sperinde, Jeffery J; Szoka Jr, Francis C (2005) Identification of a deoxyribonuclease I inhibitor from a phage-peptide library. Mol Cells 19:54-9|
|Sperinde, J J; Choi, S J; Szoka Jr, F C (2001) Phage display selection of a peptide DNase II inhibitor that enhances gene delivery. J Gene Med 3:101-8|