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Neoplastic Reversion Accomplished by High Efficiency Adenoviral-mediated Delivery of an Anti-ras Ribozyme

Gene Therapy Program, University of Alabama at Birmingham, Birmingham, Alabama 35294 [M. F., G. C., J. D., D. C.], and City of Hope National Medical Center, Duarte, California 91010 [K. S.]

Strategies have been developed to abrogate the aberrant expression of dominant oncogenes as a means to accomplish targeted tumor eradication. We have demonstrated previously the utility of this approach using a hammerhead ribozyme designed to cleave the mutant sequence in codon 12 of the activated H-ras oncogene transcript. To develop this strategy into a practical means to approach malignant disease, methods must be developed to accomplish high efficiency delivery of the ribozyme to target neoplastic cells. To accomplish this, a recombinant adenovirus was designed that encoded a gene cassette for the H-ras ribozyme. By using this virus, it was possible to accomplish high efficiency reversion of the neoplastic phenotype in mutant H-ras expressing tumor cells without the need for any selection steps. The demonstration of the utility of adenoviral-mediated delivery of anticancer ribozymes will allow the practical development of gene therapy strategies on this basis.

¹ To whom requests for reprints should be addressed, at Gene Therapy Program, University of Alabama at Birmingham, 1824 6th Avenue South, Room WTI 620, Birmingham, AL 35294-3300.

Received 2/ 9/95. Accepted 4/ 4/95.

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