Nonviral gene therapies hold great promise for the treatment of genetic and acquired diseases. However, increasing the efficiency of delivery and gene expression while reducing the inflammatory response remains a challenge. A recent study provided evidence that increased gene expression and decreased immune response result from sequentially injecting lipid and then DNA into mice, as opposed to delivering them simultaneously as a complex. It is hypothesized that the complexes formed when lipid and DNA are injected sequentially differ in structure and/or composition of bound serum proteins, leading to the variations observed in vector efficiency and toxicity. The goal of this research is to isolate the respective complexes and study their physical characteristics (i.e., size, structural details) by electron microscopy. Proteins unique to the various complexes will be examined by 2-D gel electrophoresis and the nature and identity of the proteins will be determined using mass spectroscopy. Similar studies will be performed in cationic polymer based nonviral vectors. These studies should provide useful information towards the development of new nonviral vectors with high gene expression and low immune stimulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM073514-01A1
Application #
6993857
Study Section
Special Emphasis Panel (ZRG1-F04B (20))
Program Officer
Okita, Richard T
Project Start
2005-09-22
Project End
2008-09-21
Budget Start
2005-09-22
Budget End
2006-09-21
Support Year
1
Fiscal Year
2005
Total Cost
$43,976
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599