Delivery of adenoviral vectors to the prostate for gene therapy
Delivery of adenoviral vectors to the prostate for gene therapy
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DOI：
10.1038/sj.cgt.7700011
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发表时间：
1999-01-01
影响因子：
6.4
通讯作者：
Steiner, MS
中科院分区：
文献类型：
--
作者：
Lu, Y;Carraher, J;Steiner, MS
前列腺癌已成为最常见的癌症，也是男性癌症死亡的第二大原因。一种对抗前列腺癌的新方法是基因治疗。在劳斯肉瘤病毒启动子的控制下，利用一种表达细菌β -半乳糖苷酶（β -gal） （lacZ）的复制缺陷重组腺病毒载体（AdRSVlacZ）来确定哪种递送途径最适合将腺病毒载体转导到前列腺。利用犬模型，腺病毒载体通过静脉、动脉和前列腺内（i.p）注射给药。注射后，通过(a)原位表达lacZ的细胞百分比（5-溴-4-氯-3-吲哚基β - d -半乳糖苷染色），(b) β -半乳糖酶活性（比色法β -半乳糖测定），以及(c)使用腺病毒基因组特异性引物对基因组DNA进行聚合酶链反应，测定犬前列腺和其他器官中lacZ基因的表达，以确定传播腺病毒载体的分布。与静脉注射或动脉注射（膀胱下动脉/前列腺动脉）相比，静脉注射腺病毒载体导致前列腺中lacZ的转导率和表达水平更高。因此，静脉注射（或肿瘤内）似乎是通过基于病毒的基因治疗治疗局部前列腺癌的最佳途径。
Prostate cancer has become the most frequently occurring cancer and the second leading cause of cancer deaths in men. One novel approach to combat prostate cancer is gene therapy. A replication-deficient recombinant adenoviral vector (AdRSVlacZ) expressing bacterial beta-galactosidase (beta-gal) (lacZ) under the control of the Rous sarcoma virus promoter was used to determine which delivery route was best for the transduction of adenoviral vectors to the prostate. Using a canine model, adenoviral vectors were administered by intravenous, intra-arterial, and intraprostatic (i.p.) injections. After injections, the expression of the lacZ gene was measured in canine prostates as well as in various other organs to determine the distribution of the disseminated adenoviral vector by (a) the percentage of cells expressing lacZ in situ (5-bromo-4-chloro-3-indolyl beta-D-galactoside staining), (b) beta-gal enzymatic activity (colorimetric beta-gal assay), and (c) polymerase chain reaction of genomic DNA using primers specific for the adenoviral genome. An i.p. injection of the adenoviral vector resulted in a greater transduction rate and expression level of lacZ in the prostate than either intravenous or intra-arterial (inferior vesical/prostatic artery) injections. Thus, an i.p. (or intratumoral) injection seems to be the best route to treat local regional prostate cancer by viral-based gene therapy.