Barriers to achieving stable gene therapy

实现稳定基因治疗的障碍

• 批准号: 8474804
• 负责人: James M Wilson
• 金额: $ 20.18万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8474804
• 关键词: Accounting; Address; Adenovirus Vector; Adoptive Transfer; Adult; Advisory Committees; Affect; Age; Animals; Antigens; Area; Biometry; Birth; Cells; Child; Clinic; Clinical; Clinical Trials; Codon Nucleotides; Communication; Communities; Complementary DNA; Cytotoxic T-Lymphocytes; Development; Disease; Dose; Enzymes; Epitopes; Ethics; Event; Exclusion Criteria; Firefly Luciferases; Gene Transfer; Genetic; Genome; Goals; Grant; Hepatocyte; Human; Hyperammonemia; Immunology; Inflammation; Inflammatory; Informed Consent; Inherited; Institution; Instruction; Laws; Liver; Luciferases; Measurement; Measures; Metabolic; Modeling; Monkeys; Mus; Mutate; Mutation; Nature; Neonatal; Newborn Infant; Ornithine carbamoyltransferase deficiency; Parents; Partial Hepatectomy; Patients; Phase I Clinical Trials; Plasmids; Policies; Population; Pre-Clinical Model; Preparation; Process; Proliferating; Proteins; Reporting; Risk; Role; Safety; Science; Scientist; Serum; Signal Transduction; Staging; Stratification; T-Lymphocyte; Thymus Gland; Toxic effect; Transgenes; Transgenic Mice; Translations; United States National Institutes of Health; Work; adeno-associated viral vector; anergy; autonomously replicating sequence; base; cellular transduction; clinical application; clinical efficacy; enzyme deficiency; gene therapy; hepatoma cell; immunotoxicity; inclusion criteria; liver cell proliferation; liver transplantation; liver xenograft; mouse model; mutant; operation; phase 1 study; preference; programs; promoter; transgene expression; urea cycle; vector; vector genome

This Core will be directed by Dr. Wilson with Drs. Batshaw and Caplan serving as co-directors. The Core will provide basic administrative support to manage the financial operations ofthe program project to include oversight of accounts, purchasing, and preparation and submission of reports to the institution, as well as to the NIH. An External Scientific Advisory Committee (ESAC) will be convened, which will include scientists knowledgeable about areas relevant to the grant including immunology, urea cycle disorders, AAV and vector safety assessment. An Ethics Advisory Board (EAB) will also be convened and chaired by Dr. Caplan. This Board will include a scientist from the ESAC, as well as parents of children with inherited diseases and people with expertise in ethics, policy, and law. The ESAC and EAB will convene on an annual basis to review the progress ofthe science and help the team address important issues related to the ultimate clinical applications of gene therapy. Issues that will be considered by the EAB include target cell populations for early clinical trials, informed consent, inclusion and exclusion criteria, subject recruitment and communication with the community. The Core will also provide support in biostatistics from Dr. Robert McCarter.

该核心将由 Wilson 博士和 Drs. 指导。巴特肖和卡普兰担任联合导演。核心将提供基本的行政支持来管理该计划项目的财务运作，包括监督账户、采购、准备并向该机构以及美国国立卫生研究院提交报告。将召集一个外部科学咨询委员会（ESAC），其中包括熟悉与资助相关领域的科学家，包括免疫学、尿素循环障碍、AAV 和载体安全评估。卡普兰博士还将召集并担任道德咨询委员会 (EAB) 的主席。该委员会将包括一名来自 ESAC 的科学家，以及患有遗传性疾病的儿童的父母以及具有道德、政策和法律专业知识的人士。 ESAC 和 EAB 将每年召开一次会议，审查科学进展，并帮助团队解决与基因治疗最终临床应用相关的重要问题。 EAB 将考虑的问题包括早期临床试验的目标细胞群、知情同意、纳入和排除标准、受试者招募以及与社区的沟通。该核心还将提供罗伯特·麦卡特博士在生物统计学方面的支持。