Engelhardt J F, Yang Y, Stratford-Perricaudet L D, Allen E D, Kozarsky K, Perricaudet M, Yankaskas J R, Wilson J M
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0650.
Nat Genet. 1993 May;4(1):27-34. doi: 10.1038/ng0593-27.
We describe the use of a human bronchial xenograft model for studying the efficiency and biology of in vivo gene transfer into human bronchial epithelia with recombinant E1 deleted adenoviruses. All cell types in the surface epithelium except basal cells efficiently expressed the adenoviral transduced recombinant genes, lacZ and CFTR, for 3-5 weeks. Stable transgene expression was associated with high level expression of the early adenoviral gene, E2a, in a subset of transgene expressing cells and virtually undetectable expression of the late adenoviral genes encoding the structural proteins, hexon and fiber. These studies begin to address important issues that relate to safety and in vivo efficacy of recombinant adenoviruses for gene delivery into the human airway.
我们描述了一种人类支气管异种移植模型的应用，该模型用于研究用重组E1缺失腺病毒将基因体内转移至人类支气管上皮的效率和生物学特性。表面上皮中除基底细胞外的所有细胞类型，均可在3至5周内高效表达腺病毒转导的重组基因lacZ和CFTR。稳定的转基因表达与早期腺病毒基因E2a在一部分转基因表达细胞中的高水平表达相关，而编码结构蛋白六邻体和纤维的晚期腺病毒基因的表达几乎检测不到。这些研究开始解决与重组腺病毒用于向人类气道进行基因递送的安全性和体内疗效相关的重要问题。
