腺病毒介导的核酶在小鼠中的表达。
Adenovirus-mediated expression of ribozymes in mice.
作者信息
Lieber A, Kay M A
机构信息
Markey Molecular Medicine Center, Division of Medical Genetics, Department of Medicine, University of Washington, Seattle 98195, USA.
出版信息
J Virol. 1996 May;70(5):3153-8. doi: 10.1128/JVI.70.5.3153-3158.1996.
Abstract
Ribozymes are a new pharmaceutical class of reagents that offer potential in treating a number of different medical disorders, including infectious diseases and cancer. As a first step towards using ribozymes for the treatment of liver disorders such as viral hepatitis, adenovirus vectors that contain a ribozyme expression cassette under the control of different promoters directed against human growth hormone (hGH) were 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. Furthermore, 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.
摘要
核酶是一类新型的药物试剂，在治疗多种不同的医学病症方面具有潜力，包括传染病和癌症。作为将核酶用于治疗肝脏疾病（如病毒性肝炎）的第一步，构建了含有在不同启动子控制下针对人生长激素（hGH）的核酶表达盒的腺病毒载体，并将其注入从胃肠道和肝脏产生hGH的转基因小鼠体内。在转基因小鼠模型中，腺病毒介导的表达核酶的转移在数周内使肝脏hGH mRNA减少了高达96%。此外，核酶RNA的浓度与hGH mRNA减少的程度相关。这项研究清楚地表明，核酶在体细胞基因转移后能在完整器官的表达期内发挥作用。
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