Delivery of adenoviral vectors to the prostate for gene therapy

被引:38
|
作者
Lu, Y [1 ]
Carraher, J [1 ]
Zhang, Y [1 ]
Armstrong, J [1 ]
Lerner, J [1 ]
Rogers, WP [1 ]
Steiner, MS [1 ]
机构
[1] Univ Tennessee, Coll Med, Dept Urol, Urol Res Labs, Memphis, TN 38163 USA
关键词
gene therapy; prostate; adenovirus; beta-galactosidase (lacZ);
D O I
10.1038/sj.cgt.7700011
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:64 / 72
页数:9
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