Gene therapy and enzyme replacement for Batten disease

描述（由申请人提供）：该提案侧重于影响D中枢神经系统的溶酶体贮积病的基因治疗方法。使用晚期婴儿神经元蜡样质脂褐质沉积症（LINCL / Batten病）作为D模型疾病，我建议测试关于将基因递送到小鼠疾病D模型的CNS的假设。来自我们实验室的最新数据显示，腺相关病毒4型（AAV 4）有效地指导溶酶体酶在小鼠脑中的广泛分布，这是一个令人兴奋的发现，因为D LINCL患者表现出广泛的CNS病理学。这里将测试AAV 4在LINCL的小鼠D模型中指导基因转移的能力。此外，我建议开发一种四环素调控的病毒载体，因为基因转移的临床应用可能需要调控表达以最大限度地减少免疫反应C或其他不良反应。一个受调控的载体也将使我能够解决D停止酶表达后的益处持续时间。

DESCRIPTION (provided by applicant): This proposal is focused on gene therapy approaches for lysosomal storage diseases affecting the D central nervous system. Using late infantile neuronal ceroid lipofuscinosis (LINCL / Batten Disease) as a D model disease, I propose to test hypotheses regarding delivery of a gene to the CNS of a murine disease D model. Recent data from our lab shows that adeno-associated virus type 4 (AAV4) is effective in directing D widespread distribution of a lysosomal enzyme in the murine brain, which is an exciting finding given that D LINCL patients exhibit widespread CNS pathology. The ability of AAV4 to direct gene transfer in a mouse D model of LINCL will be tested here. In addition, I propose to develop a tetracycline-regulated viral vector as I clinical applications of gene transfer will likely require regulated expression to minimize immune responses C or other adverse effects. A regulated vector will also allow me to address the duration of benefits after D cessation of enzyme expression.