Percutaneous arterial gene transfer in a rabbit model. Efficiency in normal and balloon-dilated atherosclerotic arteries.
The possibility of using an exclusively percutaneous strategy to deliver foreign DNA to normal and balloon-dilated atherosclerotic arteries was studied by analysis of transfection efficiency in a rabbit model. A total of 22 external iliac arteries from 22 rabbits (10 normal and 12 atherosclerotic) were transfected with a solution of luciferase expression vector plasmid and liposome, using a dual balloon-catheter system. Analysis of the transfected segments revealed luciferase activity in 10 of the 22 arteries (4/10 normal vs 6/12 balloon-injured atherosclerotic, P = NS); no activity could be detected in the contralateral limb arterial segments used as controls. Luciferase activity levels in successfully transfected segments measured 4.10 +/- 1.19 (m +/- SEM) Turner light units (TLU), with 3.03 +/- 1.16 TLU found in normals vs 4.81 +/- 1.87 TLU in balloon-injured atherosclerotic arteries (P = NS). In situ hybridization of successfully transfected atherosclerotic sections showed expression of the luciferase gene mRNA from rare cells (less than 1/1,000) limited to the neointimal lesion. Thus, expression of new genetic material may be achieved in both normal and balloon-dilated atherosclerotic arteries following an exclusively percutaneous approach. The low efficiency of the current delivery strategy, however, represents a potential limitation that must be improved if this strategy is to be applied as a therapeutic approach to human vascular disease.
Leclerc
G
G
Department of Medicine (Cardiology), St. Elizabeth's Hospital, Tufts University School of Medicine, Boston, Massachusetts 02135.
Gal
D
D
Takeshita
S
S
Nikol
S
S
Weir
L
L
Isner
J M
JM
D000792:Angiography; D000800:Angioplasty, Balloon; D000818:Animals; D001158:Arteries / Q000473:pathology; D001161:Arteriosclerosis / Q000628:therapy*; D008081:Liposomes / Q000008:administration & dosage; D008156:Luciferases / Q000032:analysis / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D011817:Rabbits; D014162:Transfection
D008081:Liposomes; D008156:Luciferases