Gene Therapy Approaches for Primary Immunodeficiencies

原发性免疫缺陷的基因治疗方法

• 批准号: 6433668
• 负责人: Fabio Candotti
• 金额: --
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 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/6433668
• 关键词: Wiskott Aldrich syndrome; clinical research; gene therapy; hematopoietic stem cells; human tissue; hypogammaglobulinemia; immunodeficiency; lymphocyte; severe combined immunodeficiency; technology /technique development; transfection /expression vector

Primary immunodeficiency diseases represent an unique model to study the development on the human immune system. For several of these diseases, the only currently available therapy is allogeneic bone marrow transplantation, which may result in incomplete reconstitution of immunity and may be associated with severe graft versus host reactions. Genetic correction of autologous hematopoietic stem cells would thus represent a beneficial alternative form of treatment for those immunodeficiencies of known genetic origin. We are developing pre-clinical models of gene therapy for several immunodeficiencies including X-linked severe combined immunodeficiency (X-SCID), JAK3- SCID, Wiskott-Aldrich syndrome, X-linked agammaglobulinemia, IL-12 receptor deficiency, and others. In these experiments, retroviral or non-viral vectors are being used to correct the genetic aberration responsible for each specific disorder and to express the missing or mutated protein in cells obtained from affected patients. For those immunodeficiencies for which animal models are available, experiments of genetic correction of bone marrow hematopoietic progenitors are performed to verify in vivo safety and efficacy of this approach. - Immunodeficiency, SCID, Gene Therapy, Stem cells, Lymphocytes, Genetic Vectors, Bone Marrow, Hematology, Immunology, Pediatric Research

原发性免疫缺陷疾病代表了研究人类免疫系统发展的独特模型。对于其中几种疾病，目前唯一可用的治疗是同种异体骨髓移植，这可能导致免疫的重新建立不完全，并且可能与严重的移植物与宿主反应有关。因此，自体造血干细胞的遗传校正将代表一种有益的替代形式的治疗形式，用于已知遗传起源的免疫缺陷。我们正在开发几种免疫缺陷的基因治疗前临床模型，包括X连锁的严重组合免疫缺陷（X-SCID），JAK3- SCID，Wiskott-Aldrich综合征，X连锁的agammagloblobloblobloblobloblobloblobloinemia，IL-12受体缺乏症等。在这些实验中，正在使用逆转录病毒或非病毒载体来纠正负责每种特定疾病的遗传像差，并表达受影响患者获得的细胞中缺失或突变的蛋白质。对于可用动物模型的免疫缺陷，进行了骨髓造血祖细胞的遗传校正实验，以验证这种方法的体内安全性和功效。 - 免疫缺陷，SCID，基因治疗，干细胞，淋巴细胞，遗传载体，骨髓，血液学，免疫学，儿科研究