IN VIVO ADA GENE DELIVERY FOR THE TREATMENT OF SCID

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 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. 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.