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Journal of Virology, September 1999, p. 7745-7751, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Adenovirus-Mediated Expression of a Ribozyme to c-myb mRNA Inhibits Smooth Muscle Cell Proliferation and Neointima Formation In Vivo

Dennis G. Macejak,1,* Hua Lin,2 Saiphone Webb,1 Jennifer Chase,1 Kristi Jensen,1 Thale C. Jarvis,1 Jeffrey M. Leiden,2 and Larry Couture1,dagger

Ribozyme Pharmaceuticals, Inc., Boulder, Colorado 80301,1 and Departments of Medicine and Pathology, University of Chicago, Chicago, Illinois 606372

Received 16 March 1999/Accepted 18 May 1999

Smooth muscle cell (SMC) proliferation is an important component of restenosis in response to injury after balloon angioplasty. Inhibition of proliferation in vivo can limit neointima hyperplasia in animal models of restenosis. Ribozymes against c-myb mRNA have been shown to be effective inhibitors of SMC proliferation in vitro. The effectiveness of adenovirus as a gene therapy vector in animal models of restenosis is well documented. In order to test the utility of ribozymes to inhibit SMC proliferation by a gene therapy approach, recombinant adenovirus expressing ribozymes against c-myb mRNA was generated and tested both in vitro and in vivo. This adenovirus ribozyme vector is shown to inhibit SMC proliferation in culture and neointima formation in a rat carotid artery balloon injury model of restenosis.

* Corresponding author. Mailing address: 2950 Wilderness Place, Boulder, CO 80301. Phone: (303) 546-8153. Fax: (303) 449-6500. E-mail: macejad{at}rpi.com.

dagger Present address: City of Hope National Medical Center, Duarte, CA 91010.

Journal of Virology, September 1999, p. 7745-7751, Vol. 73, No. 9
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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