MATURATION DEPENDENT ADENOVIRAL INFECTIVITY OF MYOFIBERS

越来越多的注意力集中在骨骼肌作为靶点 用于基因转移的组织，既用于生产蛋白质， 用于肌肉疾病的治疗剂和非肌肉疾病的全身递送 proteins.虽然新的突变肌肉蛋白的工程和 非肌肉蛋白质的全身递送。虽然工程的 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，病毒载体不能 有效地发育成熟的肌肉纤维仍然是一个主要的障碍， 基因转移在骨骼肌中的应用源自我们的 实验室和其他人已经显示腺病毒有效地转导 新生儿肌肉;然而，在小鼠发育的几天内， 肌肉很大程度上被折射到腺病毒转导。我们在此报告了 一系列初步结果和拟议的研究方案，旨在 定义了成熟肌肉腺病毒转导的障碍。我们 然后计划研究可以消除这些障碍的方法 克服拟议的研究应界定和消除一个主要的 病毒基因导入骨骼肌的应用障碍 以使基于肌肉的基因治疗能够有效地应用于 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.