SECOND GENERATION ADENOVIRUS AND VASCULAR GENE TRANSFER

Project: Research project

Project Details

Description

DESCRIPTION: (Adapted from the application) Gene transfer technology is
under intense evaluation for gene therapy, but its real promise may be as a
tool for investigating the molecular and cellular mechanisms of vascular
disease. Gene transfer using adenoviral vectors has been successful in
treating neointimal proliferation following vascular balloon injury, but the
vector itself induces substantial inflammation and cellular proliferation.
Fortunately, second generation adenoviral vectors have substantially reduced
viral replication and structural gene expression, and therefore, may
represent nearly inert gene transfer vectors. Accordingly, the PI will
study the effect of these newer vectors on vascular gene transfer,
determining their effect on acute and chronic inflammation and their ability
to effect long-term vascular transgene expression. Subsequently, he will
use this vector to investigate the origin and subsequent effects of
endothelial dysfunction that is present in the earliest phases of the
atherogenic process in cholesterol-fed rabbits. Specifically, he will
determine whether adenoviral transfer of genes designed to enhance vascular
nitric oxide or reduce superoxide will favorably affect the atherosclerotic
process. The proposed studies will establish the degree to which
second-generation adenoviral vectors improve upon first-generation vectors,
and will define the extent of problems that remain. In addition, the
proposed studies will use adenoviral gene transfer as a tool to enhance
understanding of the early phases of atherosclerosis. The achievement of
these goals will contribute to our understanding of atherosclerosis
atherogenesis, and increase the likelihood that vascular gene therapy will
prove to be an effective option for treatment of human atherosclerosis.
StatusNot started