Gene therapy and enzyme replacement for Batten disease

描述（由申请人提供）：本提案的重点是影响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样脂褐质病（LINCL / Batten病）作为D模型疾病，我建议测试关于基因传递到小鼠疾病D模型的中枢神经系统的假设。我们实验室最近的数据显示，腺相关病毒4型（AAV4）可以有效地指导D型溶酶体酶在小鼠大脑中的广泛分布，这是一个令人兴奋的发现，因为D型LINCL患者表现出广泛的中枢神经系统病理。本文将测试AAV4在小鼠白血病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节的病毒载体，因为基因转移的临床应用可能需要调节表达以最小化免疫反应C或其他不良反应。一个受调节的载体也将使我能够解决D停止酶表达后获益的持续时间。

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.