Abstract

The research and development of genetic delivery for treatment of ischemic heart disease is the focus of many investigations. However current techniques of gene delivery are inefficient and very limited in scope. The objective of the proposed studies is to develop a biodegradable polymer-based DNA delivery system for sustained release of vascular endothelial growth factor (VEGF) to promote revascularization in ischemic myocardium. Specifically, the applicant proposes to: encapsulate DNA in small nanometer diameter particles with a poly-lactic-polyglycolic acid co-polymer, assess the in vitro delivery mechanism of nanoparticles using beta -galactosidase as a model reporter gene, and then finally to evaluate the efficacy of VEGF gene transfer in a rat cardiac injection model. These experiments may help establish the feasibility of using this delivery system for gene therapy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL065175-03
Application #
6390777
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Liang, Isabella Y
Project Start
1999-09-27
Project End
2004-08-31
Budget Start
2001-09-01
Budget End
2004-08-31
Support Year
3
Fiscal Year
2001
Total Cost
$241,589
Indirect Cost

  Institution

Name
State University New York Stony Brook
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794

  Publications

Olson, Lyle J; Arruda-Olson, Adelaide M; Somers, Virend K et al. (2008) Exercise oscillatory ventilation: instability of breathing control associated with advanced heart failure. Chest 133:474-81
Azeloglu, Evren U; Yun, Yang H; Saltman, Adam E et al. (2006) High resolution mechanical function in the intact porcine heart: mechanical effects of pacemaker location. J Biomech 39:717-25
Kim, Angela P; Yellen, Paige; Yun, Yang H et al. (2005) Delivery of a vector encoding mouse hyaluronan synthase 2 via a crosslinked hyaluronan film. Biomaterials 26:1585-93
Yun, Yang H; Jiang, Hongliang; Chan, Rosemarie et al. (2005) Sustained release of PEG-g-chitosan complexed DNA from poly(lactide-co-glycolide). J Biomater Sci Polym Ed 16:1359-78
Jiang, Hongliang; Fang, Dufei; Hsiao, Benjamin S et al. (2004) Optimization and characterization of dextran membranes prepared by electrospinning. Biomacromolecules 5:326-33
Jiang, Hongliang; Fang, Dufei; Hsiao, Benjamin et al. (2004) Preparation and characterization of ibuprofen-loaded poly(lactide-co-glycolide)/poly(ethylene glycol)-g-chitosan electrospun membranes. J Biomater Sci Polym Ed 15:279-96
Yun, Yang H; Goetz, Douglas J; Yellen, Paige et al. (2004) Hyaluronan microspheres for sustained gene delivery and site-specific targeting. Biomaterials 25:147-57
Kim, Angela; Checkla, Daniel M; Dehazya, Philip et al. (2003) Characterization of DNA-hyaluronan matrix for sustained gene transfer. J Control Release 90:81-95
Winnicki, M; Phillips, B G; Accurso, V et al. (2001) Independent association between plasma leptin levels and heart rate in heart transplant recipients. Circulation 104:384-6