摘要
勃起功能障碍(ED)是一种常见的健康状况,发生在大约50%的老年男性(40-70岁)。近年来,人们对ED的基因治疗有了一定的关注,进一步将基因治疗理念应用到ED治疗中有着重要的意义。本文试图分析主要的挑战,并强调主要领域,包括临床前和少数临床试验,细胞靶点,以及不同的病毒载体/纳米粒在ED中的基因传递。虽然RNA干扰(RNAi)可以抑制靶基因的过度表达,但这些机制的下调与ED有关。尽管许多ED患者显示了磷酸二酯酶5型抑制剂的有效性,但这种治疗在大约30-40%的患者中是不够的。虽然对ED治疗的一些临床前研究提供了有希望的结果,但基因治疗在临床实践中并没有取得成功,部分原因是基因治疗在解决ED发病机制方面的技术局限性。小RNA的发展,如小干扰RNA(SiRNA),可能会给ED的治疗带来很大的益处。此外,将siRNA导入海绵体似乎是一个具有挑战性的问题,有待进一步发展。在ED治疗中广泛应用基因治疗之前,需要对基因治疗、基因获取、制备和传递的几个安全问题进行持续的研究。
关键词: 勃起功能障碍,基因治疗,病毒载体,车辆系统,编辑技术,心血管疾病。
Current Gene Therapy
Title:Destination Penis? Gene Therapy as a Possible Treatment for Erectile Dysfunction
Volume: 18 Issue: 4
关键词: 勃起功能障碍,基因治疗,病毒载体,车辆系统,编辑技术,心血管疾病。
摘要: Erectile Dysfunction (ED) is a common health condition occuring in roughly 50% of aging males (40-70 years old). Recent attention has related gene therapy to ED, and now there is an interest to further implement gene therapy concepts to ED treatment. This review is an attempt to analyze key challenges and emphasize primary areas, including mostly preclinical and a few clinical trials, cellular target(s), and different viral vectors/nanoparticles for gene delivery in ED. While overexpression of target genes can be silenced by RNA interference (RNAi), down-regulation of these mechanisms has been implicated in ED. Although many patients with ED demonstrate efficacy with phosphodiesterase type 5 inhibitors, this therapy is insufficient in approximately 30-40% of patients. Although several preclinical studies for ED treatment provided promising results, gene therapy has not shown success in clinical practice, due in part to technical limitations of gene therapy to address ED pathogenesis. Developments in small RNA, such as small interfering RNA (siRNA) may lead to significant benefit in the management of ED. Also, siRNA delivery into the corpus cavernosum seems a challenging issue and awaits further development. Several safety concerns of gene therapy, gene acquisition, preparation, and delivery are necessary to continue investigation before any widespread application is used in ED treatment.
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Destination Penis? Gene Therapy as a Possible Treatment for Erectile Dysfunction, Current Gene Therapy 2018; 18 (4) . https://dx.doi.org/10.2174/1566523218666180730110432
DOI https://dx.doi.org/10.2174/1566523218666180730110432 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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