• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Molecular Therapy >Suprachoroidal Electrotransfer: A Nonviral Gene Delivery Method to Transfect the Choroid and the Retina Without Detaching the Retina
【2h】

Suprachoroidal Electrotransfer: A Nonviral Gene Delivery Method to Transfect the Choroid and the Retina Without Detaching the Retina

机译：脉络膜上电转移：一种非病毒基因传递方法可在不分离视网膜的情况下转染脉络膜和视网膜

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Photoreceptors and retinal pigment epithelial cells (RPE) targeting remains challenging in ocular gene therapy. Viral gene transfer, the only method having reached clinical evaluation, still raises safety concerns when administered via subretinal injections. We have developed a novel transfection method in the adult rat, called suprachoroidal electrotransfer (ET), combining the administration of nonviral plasmid DNA into the suprachoroidal space with the application of an electrical field. Optimization of injection, electrical parameters and external electrodes geometry using a reporter plasmid, resulted in a large area of transfected tissues. Not only choroidal cells but also RPE, and potentially photoreceptors, were efficiently transduced for at least a month when using a cytomegalovirus (CMV) promoter. No ocular complications were recorded by angiographic, electroretinographic, and histological analyses, demonstrating that under selected conditions the procedure is devoid of side effects on the retina or the vasculature integrity. Moreover, a significant inhibition of laser induced-choroidal neovascularization (CNV) was achieved 15 days after transfection of a soluble vascular endothelial growth factor receptor-1 (sFlt-1)-encoding plasmid. This is the first nonviral gene transfer technique that is efficient for RPE targeting without inducing retinal detachment. This novel minimally invasive nonviral gene therapy method may open new prospects for human retinal therapies.
机译：在眼基因治疗中，靶向光感受器和视网膜色素上皮细胞（RPE）仍然具有挑战性。通过视网膜下注射给药时，病毒基因转移是达到临床评估的唯一方法，仍然引起安全隐患。我们已经开发了一种在成年大鼠中的新型转染方法，称为脉络膜上电转移（ET），该方法将非病毒质粒DNA的给药与电场作用相结合。使用报告质粒优化注射，电参数和外部电极的几何形状，可导致大面积转染组织。使用巨细胞病毒（CMV）启动子时，不仅脉络膜细胞而且RPE和潜在的感光细胞都被有效地转导了至少一个月。血管造影，视网膜电图和组织学分析均未记录到眼部并发症，这表明在选定的条件下，该手术对视网膜或脉管系统的完整性没有副作用。此外，转染可溶性血管内皮生长因子受体1（sFlt-1）编码质粒后15天，实现了对激光诱导的脉络膜新血管形成（CNV）的显着抑制。这是第一种有效的RPE靶向而不引起视网膜脱离的非病毒基因转移技术。这种新颖的微创非病毒基因治疗方法可能为人类视网膜治疗打开新的前景。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号