IN VIVO ADA GENE DELIVERY FOR THE TREATMENT OF SCID

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 严重的联合免疫缺陷(SCID)是最极端的原发免疫缺陷，在大多数儿童中，由于压倒性感染而没有接受治疗，寿命不到1-2年。腺苷脱氨酶(ADA)缺陷的SCID约占人类SCID病例的20%，在不同的SCID基因类型中是独一无二的，因为它是缺乏酶(ADA)的结果。虽然ADA在所有组织中都有表达，但ADA酶的缺失对淋巴细胞的生存至关重要，在缺乏ADA的情况下，有毒代谢物会在淋巴细胞中积聚，导致严重的代谢紊乱和细胞死亡。这些研究的目的是评估媒介在婴儿猴体内的药代动力学、剂量学和生物分布，作为在人类婴儿试验之前的临床前研究。这些研究对于将这一方法转化为人类ADA缺乏的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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.