Brody S L, Crystal R G
Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
Ann N Y Acad Sci. 1994 May 31;716:90-101; discussion 101-3. doi: 10.1111/j.1749-6632.1994.tb21705.x.
Adenovirus vectors are efficient vehicles for in vivo gene transfer to many different cell types. Recombinant adenovirus vectors containing exogenous genes for transfer are derived from adenovirus type 5 and are made replication deficient by the deletion of the E1 region. Based on the observation that many natural adenovirus infections are targeted to airway epithelial cells, a replication-deficient adenovirus vector was constructed containing the cystic fibrosis transmembrane conductance regulator cDNA for the potential therapy of the respiratory manifestations of cystic fibrosis. Using this vector, the normal human CFTR cDNA has been successfully transferred to airway epithelial cells of experimental animals via the trachea. This finding has led to the development of human gene therapy protocols for the evaluation of the safety and efficacy of adenovirus-mediated CFTR cDNA transfer to lungs of individuals with cystic fibrosis. In addition to the airways, adenovirus vectors have been demonstrated to mediate in vivo gene delivery to cells of the liver, blood vessels, brain, muscle, heart, peritoneum, and salivary glands. Adenovirus vectors containing marker genes have also been demonstrated to transfer genes to human tumor cells in nude mice. Such vectors may be useful for a variety of therapeutic applications for in vivo gene transfer for the therapy of cancer and other diseases.
腺病毒载体是将基因在体内转移至多种不同细胞类型的有效载体。含有用于转移的外源基因的重组腺病毒载体源自5型腺病毒，并通过缺失E1区域而使其复制缺陷。基于许多天然腺病毒感染靶向气道上皮细胞这一观察结果，构建了一种复制缺陷型腺病毒载体，其包含囊性纤维化跨膜传导调节因子cDNA，用于潜在治疗囊性纤维化的呼吸道表现。使用该载体，已通过气管将正常人CFTR cDNA成功转移至实验动物的气道上皮细胞。这一发现促使了人类基因治疗方案的发展，以评估腺病毒介导的CFTR cDNA转移至囊性纤维化患者肺部的安全性和有效性。除了气道外，腺病毒载体已被证明可介导在体内将基因递送至肝脏、血管、脑、肌肉、心脏、腹膜和唾液腺的细胞。含有标记基因的腺病毒载体也已被证明可将基因转移至裸鼠体内的人类肿瘤细胞。此类载体可能对用于癌症和其他疾病治疗的多种体内基因转移治疗应用有用。
