Zabner J, Petersen D M, Puga A P, Graham S M, Couture L A, Keyes L D, Lukason M J, St George J A, Gregory R J, Smith A E
Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242.
Nat Genet. 1994 Jan;6(1):75-83. doi: 10.1038/ng0194-75.
Gene therapy for cystic fibrosis (CF) will require the safe transfer of CFTR cDNA to airway epithelia in vivo. We showed previously that a recombinant adenovirus, Ad2/CFTR-1, expresses CFTR in vitro. As adenovirus rarely integrates, treatment will require repeated vector administration. We applied Ad2/CFTR-1 to intrapulmonary airway epithelia of cotton rats and nasal epithelia of Rhesus monkeys. In both species we detected CFTR mRNA and protein after repeated administration and in monkeys, protein was detected six weeks after repeat administration. The vector did not replicate and was rapidly cleared. Despite an antibody response, there was no evidence of a local or systemic inflammatory response after repeat administration. These data indicate that repetitive administration of Ad2/CFTR-1 is both safe and efficacious.
囊性纤维化（CF）的基因治疗需要将CFTR cDNA安全地导入体内气道上皮细胞。我们之前已表明，重组腺病毒Ad2/CFTR-1在体外可表达CFTR。由于腺病毒很少整合，治疗需要反复给予载体。我们将Ad2/CFTR-1应用于棉鼠的肺内气道上皮细胞和恒河猴的鼻上皮细胞。在这两个物种中，反复给药后均检测到CFTR mRNA和蛋白质，在恒河猴中，反复给药六周后检测到蛋白质。载体未复制并迅速清除。尽管有抗体反应，但反复给药后没有局部或全身炎症反应的证据。这些数据表明，反复给予Ad2/CFTR-1既安全又有效。
