Inhibition of proliferation of vascular smooth muscle cell

Details Inhibition of proliferation of vascular smooth muscle cell Inhibition of proliferation of vascular smooth muscle cell

A - Human Necessities

61

K

A61K 31/70 (2006.01) A61K 9/127 (2006.01) C12N 15/11 (2006.01)

Patent

CA 2163234

This invention encompasses a method for inhibiting vascular cellular activity of cells associated with vascular lesion formation in mammals which involves administering an effective dosage of at least one antisense sequence to at least one gene expressing a cyclin or a cyclin dependent kinase which inhibits the expression of the gene. More particularly, the invention involves administering antisense sequences which inhibit the expression of cyclin A, B1, B2, C, D1, D2, D3, E or cyclin X (p46) and cyclin dependent kinase cdc2, cdk2, cdk4 or cdk5. It is preferable to use two antisense sequences each from a different cyclin or cyclin dependent kinase. The cyclin or cyclin depending kinase dosage is preferably administered in combination with proliferating cell nuclear antigen (PCNA). Antisense methods and compositions direct to inhibiting the expression of growth factors such as TGF-.beta.1, TGF, bFGF, PDGF are also contemplated by the present invention. The antisense sequences are incorporated into liposomes, particularly liposomes containing HVJ and which are directly administered intraluminally, intramurally or periadventitiously. While the methods of this invention are useful in treating a broad spectrum of vascular lesions such as lesions in the carotid femural and renal arteries, particularly lesions resulting from renal dialysis fistulas. The invention is particularly useful in treating vascular lesions associated with coronary artery angioplasty.

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