Lentiviral Vector for the treatment of Fanconi Anemia

治疗范可尼贫血的慢病毒载体

基本信息

批准号：
9126592
负责人：
William Scott Goebel
金额：
$ 29.33万
依托单位：
RIMEDION, INC.
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9126592
关键词：
Agreement Allogenic Animal Model Animals Applications Grants Area Autologous Biological Assay Biology Blood Circulation Businesses CD34 gene Cells Childhood Clinic Clinical Clinical Protocols Clinical Trials Clinical Trials Design Collaborations Cyclophosphamide DNA Repair Defect Development Disease Dose Failure Fanconi Anemia Complementation Group A Protein Fanconi&apos s Anemia Funding Gene Transfer Genes Goals Growth HIV-1 Health Hematological Disease Hematopoietic Stem Cell Transplantation Hematopoietic System Hematopoietic stem cells Hemophilia A Hereditary Disease Homologous Transplantation Immunologic Deficiency Syndromes In Vitro Incidence Indiana Infusion procedures Intravenous Investigational New Drug Application Lentivirus Vector Licensing Malignant Neoplasms Marrow Methods Mutation National Heart, Lung, and Blood Institute Non-Hematologic Malignancy Other Genetics Pancytopenia Parents Patients Phase Population Predisposition Production Proteins Published Comment Rare Diseases Recording of previous events Regimen Research Personnel Risk Route Safety Sampling Siblings Sickle Cell Anemia Small Business Technology Transfer Research Stem cells Technology Technology Transfer Testing Thalassemia Time Transplantation United States National Institutes of Health Universities Validation Vesicular stomatitis Indiana virus Work base cellular transduction chemotherapy commercialization design experience gene correction gene discovery gene therapy innovation interest mouse model novel novel strategies phase I trial prevent stem therapeutic gene vector

项目摘要

DESCRIPTION (provided by applicant): In this Phase II STTR application Rimedion seeks to commercialize a novel treatment for patients suffering from Fanconi anemia and request funding for a Phase I/II clinical trial. The product will utilize a HIV-1 based lentiviral vector expressin the Fanconi anemia A protein. The strong scientific support for this approached is strengthened by a successful Phase I STTR. The proposal is highly responsive to the PA-13- 235 PHS 2014-02 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR[R41/R42]) and the area of interest for NHLBI (HLS13-04). The clinical trial will be open at Indiana University and brings together a combined experience in the biology of Fanconi anemia, gene therapy, and hematopoietic stem cell transplantation. Fanconi Anemia (FA) is a heterogeneous genetic disorder that is characterized by progressive bone marrow failure and cancer predisposition due to a deficiency in DNA repair. Animal models of FA are available and have shown that introduce a wild-type copy of the defect gene into hematopoietic stem cells can prevent marrow failure. This Phase II proposal has the following aims: Specific Aim 1. Complete Method Validation, Generate Clinical Vector Product, and Perform Additional In Vitro Immortalization Assays. Specific Aim 2: Conduct a Phase I trial in subjects with Fanconi anemia A by introducing a functioning FANCA gene into autologous CD34+ stem and progenitor cells. Cells will be treated ex vivo and reinfused into the circulation through the intravenous route.

描述（由申请人提供）：在本 II 期 STTR 申请中，Rimedion 寻求将一种针对 Fanconi 贫血患者的新型治疗方法商业化，并为 I/II 期临床试验申请资金。该产品将利用基于 HIV-1 的慢病毒载体，表达 Fanconi 贫血 A 蛋白。第一阶段 STTR 的成功为这一方法提供了强有力的科学支持。该提案高度响应 NIH 小型企业技术转让补助金申请 PA-13-235 PHS 2014-02 综合征集（母版 STTR[R41/R42]）和 NHLBI 感兴趣的领域（HLS13-04）。该临床试验将在印第安纳大学开放，汇集范可尼贫血生物学、基因治疗和造血干细胞移植方面的综合经验。范可尼贫血 (FA) 是一种异质性遗传性疾病，其特征是由于 DNA 修复缺陷导致进行性骨髓衰竭和癌症易感性。 FA 动物模型已经存在，并且表明将缺陷基因的野生型拷贝引入造血干细胞可以预防骨髓衰竭。该第二阶段提案有以下目标：具体目标 1. 完成方法验证，生成临床载体产品，并进行额外的体外永生化测定。具体目标 2：通过将功能性 FANCA 基因引入自体 CD34+ 干细胞和祖细胞中，对范可尼贫血 A 受试者进行 I 期试验。细胞将经过离体处理并通过静脉途径重新注入循环系统。