Vector Targeting for Fracture Repair

用于骨折修复的矢量靶向

• 批准号: 6441350
• 负责人: Alan ROBERT Davis
• 金额: $ 7.53万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-28 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6441350
• 关键词: adeno associated virus group; antibody; binding proteins; biotechnology; bone fracture; bone morphogenetic proteins; bone regeneration; flow cytometry; gene delivery system; gene therapy; laboratory mouse; osteoblasts; osteogenesis; protein binding; protein engineering; protein tyrosine phosphatase; receptor binding; tissue /cell culture; transfection /expression vector; virus protein; virus receptors

DESCRIPTION (provided by applicant): Many investigators have shown that adenoviral (Ad) vectors expressing the bone morphogenetic protein BMP2 can enhance fracture repair by eliciting bone formation that closely resembles the normal process, in contrast to results obtained with direct injection of the recombinant protein. Delivery of BMP2 via an Ad vector is therefore an attractive strategy for improving bone repair, which currently is delayed or unsuccessful in 5-10% of fracture cases. A major challenge is to produce a safe osteoblast-targeted vector that does not recognize cells expressing the widespread adenovirus, CAR, the usual route by which adenoviruses infect mammalian cells. This proposal seeks to increase the specificity and safety of Ad vectors by modifying the viral fiber protein (Aim 1) so that it no longer binds to CAR, but instead recognizes the OST-PTP protein on osteoblasts (Aim 2). These objectives will be pursued by ablating critical amino acid sequences in the fiber DG loop and monitoring cells for evidence of infection through the CAR-binding pathway, and by constructing vectors whose fiber carries both the CAR-binding sequence deletion and an OST-PTP-specific antibody sequence and then assessing their ability to target osteoblasts in vitro and in vivo. Vectors emerging from these studies will be prime candidates for insertion of BMP2 or other therapeutic genes with relevance to bone disease. Given the applicant's experience in adenoviral vector design and translational research in university and pharmaceutical settings, the prospects for a successful outcome of this project appear high.

描述（由申请人提供）：许多研究者已经证明