Ethanol improves adenovirus-mediated gene transfer and expression to the bladder epithelium of rodents
Ethanol improves adenovirus-mediated gene transfer and expression to the bladder epithelium of rodents
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DOI：
10.1016/s0090-4295(98)00641-4
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发表时间：
1999-05-01
期刊：
影响因子：
2.1
通讯作者：
Maneval, DC
中科院分区：
文献类型：
--
作者：
Engler, H;Anderson, SC;Maneval, DC
目标。复制缺陷腺病毒载体（rAds）被用作基因传递系统，可以有效地转导多种组织，并且可能是开发用于许多泌尿系统应用的基因治疗的合适载体。然而，膀胱上皮在囊内给药后显示出对转基因表达的高度抗性。对这种低基因转移效率的潜在解释可能是尿路上皮的保护结构。由于这种保护屏障可能被有机溶剂破坏，我们评估了乙醇联合给药是否可以增强腺病毒介导的转基因表达。正常大鼠和膀胱癌大鼠一次性囊内给予编码β -半乳糖苷酶（rAd- β gal）或p53 （rAd-p53）的rAd， rAd分别在生理盐水溶液或增加浓度的乙醇溶液中给予，观察其在膀胱组织中的转基因表达。通过在22%乙醇溶液中施用rad - β -gal，尿路上皮β -半乳糖苷酶转基因表达显著增加。在正常尿路上皮和浅表性膀胱肿瘤中，转基因表达增强。p53基因表达同样增强。在啮齿类动物的正常膀胱上皮和肿瘤膀胱上皮中，共给药22%乙醇增强了局部rad介导的转基因表达。rad介导的转基因表达的改善是向尿路上皮局部基因传递的进展，可能使浅表性膀胱癌或其他膀胱疾病的局部基因治疗成为可能。泌尿外科杂志，1999。(C) 1999, Elsevier Science Inc.；版权所有。
Objectives. Replication deficient adenoviral vectors (rAds) are used as gene delivery systems that can efficiently transduce a variety of tissues and may be appropriate vectors to develop gene therapeutics for many urologic applications. However, the bladder epithelium has been shown to be highly resistant to transgene expression after intracystic administration. A potential explanation for this low gene transfer efficiency may be the protective structure of the urothelium. Since this protective barrier can be disrupted by organic solvents, we assessed whether ethanol co-administration can enhance adenovirus-mediated transgene expression.Methods. Normal and bladder tumor-bearing rats received a single intracystic administration of rAd encoding beta-galactosidase (rAd-beta gal) or p53 (rAd-p53), rAd was administered in a saline solution or in solutions with increasing concentrations of ethanol, Transgene expression was evaluated in the bladder tissues.Results. A dramatic increase in urothelial beta-galactosidase transgene expression was achieved by rAd-beta gal administered in a 22% ethanol solution. Transgene expression was enhanced in normal urothelium and in superficial bladder tumors. p53 transgene expression was similarly enhanced.Conclusions. Co-administration of 22% ethanol enhanced local rAd-mediated transgene expression in the normal and neoplastic bladder epithelium in rodents. Improvement of rAd-mediated transgene expression is progress toward local gene delivery to the urothelium and may enable local gene therapy for superficial bladder cancer or other bladder diseases. UROLOGY 53: 1049-1053, 1999. (C) 1999, Elsevier Science Inc. All rights reserved.