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Ribozyme-mediated Modulation of Human O⁶-Methylguanine-DNA Methyltransferase Expression¹

Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101

A synthetic oligonucleotide containing ribozyme sequences targeted to the 5' region of the human O⁶-methylguanine-DNA methyltransferase (MGMT) mRNA has been constructed. This ribozyme demonstrates cleavage activity in vitro in the presence of Mg²⁺. To determine whether this ribozyme can function in vivo, HeLa CCL2 cells were transfected with a mammalian expression vector containing the ribozyme sequence. Following selection and expansion of individual transfectants, a stable clone was isolated that lacks both MGMT mRNA and protein. Molecular analysis of this cell line indicates that in vivo cleavage of MGMT mRNA is responsible for the lack of MGMT activity.

¹ This work was supported by NIH Grants CA 14799, CA 36888 and CA 23099, Cancer Center Support CORE Grant P30 CA 21765 and by the American Lebanese Syrian Associated Charities.

² To whom requests for reprints should be addressed.

Received 12/30/92. Accepted 3/ 5/93.

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