MATURATION DEPENDENT ADENOVIRAL INFECTIVITY OF MYOFIBERS

越来越多的注意力集中在作为目标的骨骼肌上 用于基因转移的组织既用于生产蛋白质，也可能是 肌肉疾病的治疗和非肌肉的全身递送 蛋白质。虽然新的突变肌肉蛋白的工程和 全身输送非肌肉蛋白。虽然工程学上的 新的突变载体减少了与病毒相关的问题 细胞毒性和免疫排斥，病毒载体无法 有效地转导成熟的肌肉纤维仍然是一个主要障碍 基因转移在骨骼肌中的应用。结果来自我们的 实验室和其他实验室已经证明，腺病毒可以有效地转导 新生肌肉；然而，在小鼠发育的几天内， 肌肉在很大程度上是对腺病毒转导的折射。在这里，我们呈现 一系列初步成果和拟议研究方案，旨在 确定成熟肌肉中腺病毒转导的障碍。我们 然后计划调查这些障碍可以被用来 克服困难。拟议的研究应该定义并消除一个主要的 病毒基因传递在骨骼肌应用面临的障碍 使以肌肉为基础的基因疗法能够有效地应用于 遗传性和获得性疾病。

Increasing attention has been focused on skeletal muscle as a target tissue for gene transfer both for the production of proteins that may be therapeutic for muscle disorders and the systemic delivery of non-muscle proteins. Although the engineering of new mutant muscle proteins and the systemic delivery of non-muscle proteins. Although the engineering of new mutant vectors has reduced the problems associated with viral cytotoxicity and immune rejection, the inability of viral vectors to efficiently transduce mature muscle fibers has remained a major barrier to the application of gene transfer to skeletal muscle. Results from our laboratory and others have shown that adenovirus efficiently transduces neonatal muscle; however, within a few days of mouse development, the muscle is largely refracted to adenoviral transduction. Here we present a series of preliminary results and proposed research protocols aimed at defining the barriers to adenoviral transduction of mature muscle. We then plan to investigate methods by which these barriers can be overcome. The proposed research should define and eliminate a major hurdle facing the application of viral gene delivery to skeletal muscle to enable efficient application of muscle-based gene therapy for both inherited and acquired diseases.