IN VIVO ADA GENE DELIVERY FOR THE TREATMENT OF SCID

用于治疗 SCID 的体内 ADA 基因递送

• 批准号: 8357305
• 负责人: Donald B Kohn
• 金额: $ 7.56万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357305
• 关键词: Accounting; Biodistribution; California; Cell Death; Child; Childhood; Drug Kinetics; Enzymes; Funding; Gene Delivery; Genetic; Grant; Human; Immune; Infant; Infection; Longevity; Lymphocyte; Metabolic; Monkeys; National Center for Research Resources; Patients; Primates; Principal Investigator; Research; Research Infrastructure; Resources; SCID Mice; Source; Testing; Tissues; Translating; United States National Institutes of Health; adenosine deaminase; cost; dosimetry; in vivo; preclinical study; vector

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Severe combined immune deficiency (SCID) represents the most extreme primary immune deficiency with a life-span of less than 1-2 years in most children without therapy due to overwhelming infections. Adenosine deaminase (ADA)-deficient SCID, which accounts for ~20% of human cases of SCID, is unique among the different genetic types of SCID in that it results from the absence of an enzyme (ADA). Although ADA is expressed in all tissues, the absence of ADA enzyme is most critical to the survival of lymphocytes and, in the absence of ADA, toxic metabolites accumulate in lymphocytes and causes severe metabolic derangements and cell death. The objective of these studies is to assess vector pharmacokinetics, dosimetry, and biodistribution in infant monkeys as pre-clinical studies prior to testing in human infants. These studies are essential to translate this approach to human ADA-deficient SCID pediatric patients.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 严重的联合免疫缺陷（SCID）代表了最极端的原发性免疫缺陷，由于压倒性感染而没有治疗的大多数儿童的生命跨度不到1-2岁。腺苷脱氨酶（ADA）缺乏SCID，占人类SCID病例的约20％，在不同的遗传类型的SCID中是独一无二的，因为它是由于缺乏酶（ADA）而引起的。 尽管ADA在所有组织中均表达，但ADA酶的缺乏对于淋巴细胞的存活最为至关重要，并且在没有ADA的情况下，有毒代谢产物积累在淋巴细胞中，并导致严重的代谢危险和细胞死亡。这些研究的目的是评估婴儿猴子作为临床前研究的载体药代动力学，剂量法和生物分布。这些研究对于将这种方法转化为人类ADA缺乏的SCID小儿患者至关重要。