IN VIVO ADA GENE DELIVERY FOR THE TREATMENT OF SCID

该子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。次级项目的主要支助 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 表示子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 严重联合免疫缺陷（SCID）是最极端的原发性免疫缺陷，由于压倒性感染，大多数儿童的寿命不到1-2年，没有治疗。腺苷脱氨酶（ADA）缺陷型SCID占人类SCID病例的约20%，在不同遗传类型的SCID中是独特的，因为它是由于缺乏酶（ADA）。 虽然ADA在所有组织中表达，但ADA酶的缺乏对淋巴细胞的存活最为关键，并且在ADA缺乏的情况下，毒性代谢物在淋巴细胞中积累并导致严重的代谢紊乱和细胞死亡。这些研究的目的是在人类婴儿中进行试验之前，作为临床前研究，评估幼猴中的载体药代动力学、剂量测定和生物分布。这些研究对于将这种方法转化为人类ADA缺陷的SCID儿科患者至关重要。

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.