将携带人囊性纤维化跨膜传导调节因子（CFTR）互补DNA（cDNA）的腺病毒施用于囊性纤维化患者的呼吸道。
Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis.
作者信息
Crystal R G, McElvaney N G, Rosenfeld M A, Chu C S, Mastrangeli A, Hay J G, Brody S L, Jaffe H A, Eissa N T, Danel C
机构信息
Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
出版信息
Nat Genet. 1994 Sep;8(1):42-51. doi: 10.1038/ng0994-42.
We have administered a recombinant adenovirus vector (AdCFTR) containing the normal human CFTR cDNA to the nasal and bronchial epithelium of four individuals with cystic fibrosis (CF). We show that this vector can express the CFTR cDNA in the CF respiratory epithelium in vivo. With doses up to 2 x 10(9) pfu, there was no recombination/complementation or shedding of the vector or rise of neutralizing antibody titres. At 2 x 10(9) pfu, a transient systemic and pulmonary syndrome was observed, possibly mediated by interleukin-6. Follow-up at 6-12 months demonstrated no long term adverse effects. Thus, it is feasible to use an adenovirus vector to transfer and express the CFTR cDNA in the respiratory epithelium of individuals with CF. Correction of the CF phenotype of the airway epithelium might be achieved with this strategy.
我们已将携带正常人囊性纤维化跨膜传导调节因子（CFTR）互补DNA（cDNA）的重组腺病毒载体（AdCFTR）施用于4名囊性纤维化（CF）患者的鼻腔和支气管上皮。我们证明该载体能够在体内CF呼吸道上皮中表达CFTR cDNA。给予高达2×10⁹ 空斑形成单位（pfu）的剂量时，未出现载体的重组/互补或脱落现象，也未出现中和抗体滴度升高。给予2×10⁹ pfu剂量时，观察到一种短暂的全身和肺部综合征，可能由白细胞介素-6介导。6至12个月的随访显示无长期不良反应。因此，使用腺病毒载体在CF患者的呼吸道上皮中转移并表达CFTR cDNA是可行的。通过该策略可能实现气道上皮CF表型的纠正。
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