ADENOVIRUS-MEDIATED EXPRESSION OF RIBOZYMES IN MICE

Ribozymes are a new pharmaceutical class of reagents that offer potent ial in treating a number of different medical disorders, including inf ectious diseases and cancer. As a first step towards using ribozymes f og the treatment of liver disorders such as viral hepatitis, adenoviru s vectors that contain a ribozyme expression cassette under the contro l of different promoters directed against human growth hormone (hGH) w ere constructed and infused into transgenic mice that produce hGH from the gastrointestinal tract and liver. Adenovirus-mediated transfer of expressed ribozymes resulted in up to a 96% reduction of hepatic hGH mRNA over a period of several weeks in the transgenic mouse model. Fur thermore, the concentration of ribozyme RNA correlated with the degree of hGH mRNA reduction. This study clearly demonstrates that ribozymes can function during the period of expression in an intact organ after somatic gene transfer.