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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK010052-02
Application #
6397743
Study Section
Special Emphasis Panel (ZRG1-BIO (01))
Program Officer
Hyde, James F
Project Start
2001-03-17
Project End
Budget Start
2001-03-17
Budget End
2002-01-27
Support Year
2
Fiscal Year
2001
Total Cost
$35,153
Indirect Cost
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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