Long term inhibition of neointima formation in balloon-injured rat arteries by intraluminal instillation of a matrix-targeted retroviral vector bearing a cytocidal mutant cyclin G1 construct

Restenosis from neointimal proliferation is a frequent complication of intr acoronary stenting and catheter-based revascularization procedures. Current ly, there is no known therapeutic strategy that has been sufficiently effec tive to warrant its widespread use. In the present study, the antiprolifera tive properties of a matrix (collagen)-targeted retroviral vector bearing a mutant cyclin G1 (DNT 41-249) construct was evaluated in vitro and in vivo . In controlled one-month efficacy studies, the intraluminal instillation o f the mutant cyclin GI vector significantly inhibited neointima lesion form ation in balloon-injured rat arteries without 'catch-up' neointimal growth, associated necrosis or intense inflammatory reaction. Taken together, thes e data extend the potential utility of the matrix-targeted mutant cyclin G1 retroviral vector for management of vascular restenosis.