AAV Mini-dystrophin Vectors for DMD Gene Therapy

用于 DMD 基因治疗的 AAV 微型肌营养不良蛋白载体

• 批准号: 7285775
• 负责人: Xiao Xiao
• 金额: $ 47.56万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7285775
• 关键词: adeno associated virus group; biotechnology; cooperative study; dystrophin; enzyme linked immunosorbent assay; gene delivery system; gene therapy; genetic techniques; genetically modified animals; laboratory mouse; muscular dystrophy; musculoskeletal disorder therapy; nonhuman therapy evaluation; polymerase chain reaction; transfection /expression vector; western blottings

DESCRIPTION (provided by applicant): The goal of this proposal is to design, test, and produce a recombinant adeno-associated viral (AAV) vector carrying a functional mini-dystrophin gene which will be extensively studied in vivo for therapeutic efficacy as well as long-term safety in animal models. The clinical grade vector will be produced in the final year for a Phase I gene therapy safety trial for Duchenne muscular dystrophy (DMD). This proposal is highly integrated, involving scientists in both basic research and clinical studies, with the objective of generating an optimized AAV vector in five years for a Phase I safety trial in DMD patients. The design, test and production of the gene vectors and the pre-clinical safety studies, as required by FDA, will be carried out at the University of Pittsburgh in collaboration with other institutions. A parallel study that is equally important for the success of the clinical trial, but through a different funding mechanism outside this proposal, will be conducted by a team led by Dr. Jerry R. Mendell at the Ohio State University, where a DMD patient cohort will be characterized at the pathological, immunological and molecular levels for future recruitment. To successfully execute this challenging translational research project, we plan to accomplish five Specific Aims. The first three Aims will be devoted to optimization of mini-dystrophin genes, selection of a small but strong muscle-specific promoter, and the investigation of gene delivery methods. The last two Aims will concentrate on preclinical vector toxicology study and clinical grade AAV vector production under the GMP conditions. The success of this grant will lead to the IND filing and RAC submission of the DMD gene therapy protocol.

描述（由申请人提供）：