摘要
Catalytic nucleic acids have been used in a reverse genetics approach to study gene function. We are interested in applying this technology to study the autosomal recessive disease Spinal Muscular Atrophy (SMA) which is caused by loss of survival motor neuron gene (SMN) product leading to progressive motor neuron loss and muscular atrophy. Although the SMN gene is ubiquitously expressed, the cause for selective motor neuron loss is unknown. Embryonal lethality in mice has made it extremely difficult to generate animal models of SMA. We describe a procedure for selecting effective DNAzymes (DZ) and ribozymes (RZ) based on their ability to cleave the full length Smn mRNA at low magnesium concentrations, after a short time period, and at a low catalytic nucleic acid to target ratio. Using these criteria three effective RZ and DZ were generated. These results indicate that catalytic nucleic acids can effectively cleave Smn target RNA in an environment closely resembling that present in the cell and thus have potential for interference with Smn gene expression in cells and in vivo. .overlined { text-decoration: overline; } .struck { text-decoration:line-through; } .underlined { text-decoration:underline; } .doubleUnderlined { text-decoration:underline;border-bottom:1px solid #000; } Enhanced Article (HTML) Get PDF (1850K)Get PDF (1850K) More content like thisFind more content: like this articleFind more content written by: Barbara Trülzsch Kay Davies Matthew Wood All Authors
摘要译文
催化核酸已经用于反向遗传学方法来研究基因功能研究常染色体隐性疾病脊髓性肌萎缩（SMA），其由导致进行性运动神经元损失和肌肉萎缩的存活运动神经元基因（SMN）产物的丧失引起虽然SMN基因无所不在地表达，选择性运动神经元损失的原因是未知的。小鼠的胎儿致死性使得极难产生SMA generate的动物模型我们描述了基于它们在低镁浓度下在短时间段后切割全长Smn mRNA的能力选择有效DNA核酶（DZ）和核酶（RZ）的程序，并且以低催化核酸与靶标比例。使用这些标准产生三种有效的RZ和DZ核酸可以在与细胞中存在的环境非常类似的环境中有效切割Smn靶RNA，因此具有干扰细胞和体内的Smn基因表达的潜力竜Verlined {text-decoration：overline; }竤truck {text-decoration：line-through; }竨nderlined {text-decoration：underline; }竏oubleUnderlined {text-decoration：underline;border-bottom：1px solid＃000;增强文章（HTML）获取PDF（1850K）获取PDF（1850K）更多内容喜欢这篇文章更多内容：喜欢本文目的更多内容写作：BarbaraTrülzschKay Davies Matthew Wood所有作者
Barbara Trülzsch[*]; Kay Davies and Matthew Wood;. Characterisation of catalytic nucleic acids targeting the survival of motor neuron messenger RNA[J]. Neuroscience Research Communications, 2003,32(2): 95-106