Improved Adenoviral Vectors for Hepatic Gene Therapy

用于肝脏基因治疗的改良腺病毒载体

• 批准号: 6873620
• 负责人: Mark A Kay
• 金额: $ 32.18万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6873620
• 关键词: biotechnology; computer assisted sequence analysis; disease /disorder model; dogs; gel electrophoresis; gene deletion mutation; gene expression; gene therapy; genome; hemophilia B; host organism interaction; integrase; laboratory mouse; liver; liver cells; nucleic acid sequence; plasmids; protein protein interaction; protein structure function; tissue /cell culture; transfection /expression vector; transposon /insertion element; virus protein; yeast two hybrid system

DESCRIPTION (provided by applicant): Recombinant adenoviral vectors have had a stormy history. Nevertheless, there is promise in the development of gene-deleted adenoviruses because of reduced toxicity, efficient gene transfer, and large DNA carrying capacity. The goal of this project is to develop scientific principles required for production and evaluation of gene-deleted adenoviral vectors that remain episomal and/or integrate into host chromosomal DNA. The new vectors will be assessed in animals for efficacy as well as safety with the primary focus being on liver gene transfer. Using DNA transposons and site-specific phage integrases, we plan to develop gone-deleted vectors that can integrate an expression cassette into the host chromosome. Both episomal and integrating gene deleted vectors will be compared for longevity of therapeutic gene expression in a dog model of hemophilia. This will allow us to establish the utility of use of the vector for treating genetic diseases where life-long gene expression is required in most situations. We will begin to attempt to unravel the molecular state of the vector DNA and identify cellular proteins that may be involved in stabilizing episomal adenoviral vector DNAs in vivo. Taken together, these studies will advance our basic understanding of vector-host interactions related to persistence of vector in rive, as well as advancing therapeutic applications in preclinical development.

描述（由申请人提供）：