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基于阳离子脂质体和微小环 DNA 技术的非病毒载体可提高基因传递效率，在视网膜疾病的生物医学应用中具有广阔的应用前景。

Non-viral vectors based on cationic niosomes and minicircle DNA technology enhance gene delivery efficiency for biomedical applications in retinal disorders.

机构信息

NanoBioCel Group, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Spain.

NanoBioCel Group, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.

出版信息

Nanomedicine. 2019 Apr;17:308-318. doi: 10.1016/j.nano.2018.12.018. Epub 2019 Feb 18.

DOI:10.1016/j.nano.2018.12.018
PMID:30790710
Abstract

Low transfection efficiency is a major challenge to overcome in non-viral approaches to reach clinical practice. Our aim was to explore new strategies to achieve more efficient non-viral gene therapies for clinical applications and in particular, for retinal diseases. Cationic niosomes and three GFP-encoding genetic materials consisting on minicircle (2.3 kb), its parental plasmid (3.5 kb) and a larger plasmid (5.5 kb) were combined to form nioplexes. Once fully physicochemically characterized, in vitro experiments in ARPE-19 retina epithelial cells showed that transfection efficiency of minicircle nioplexes doubled that of plasmids ones, maintaining good cell viability in all cases. Transfections in retinal primary cells and injections of nioplexes in rat retinas confirmed the higher capacity of cationic niosomes vectoring minicircle to deliver the genetic material into retina cells. Therefore, nioplexes based on cationic niosomes vectoring minicircle DNA represent a potential tool for the treatment of inherited retinal diseases.

摘要

非病毒方法要达到临床实践水平，克服低转染效率是一个主要挑战。我们的目的是探索新的策略，以实现更有效的非病毒基因治疗，特别是针对视网膜疾病。阳离子脂质体囊泡和三种 GFP 编码的遗传物质（包括微环（2.3kb）、其亲本质粒（3.5kb）和较大的质粒（5.5kb））被组合形成脂质体复合物。经过全面的物理化学特性分析，在 ARPE-19 视网膜上皮细胞的体外实验中表明，微环脂质体复合物的转染效率是质粒脂质体复合物的两倍，在所有情况下都保持良好的细胞活力。在原代视网膜细胞中的转染以及在大鼠视网膜中的脂质体复合物注射实验证实，阳离子脂质体囊泡载体微环具有将遗传物质递送到视网膜细胞的更高能力。因此，基于阳离子脂质体囊泡载体微环 DNA 的脂质体复合物代表了治疗遗传性视网膜疾病的潜在工具。

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