Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Biomaterials. 2013 Sep;34(29):7158-67. doi: 10.1016/j.biomaterials.2013.06.002. Epub 2013 Jun 22.
Ocular gene therapy has been extensively explored in recent years as a therapeutic avenue to target diseases of the cornea, retina and retinal pigment epithelium (RPE). Adeno-associated virus (AAV)-mediated gene therapy has shown promise in several RPE clinical trials but AAVs have limited payload capacity and potential immunogenicity. Traditionally however, non-viral alternatives have been plagued by low transfection efficiency, short-term expression and low expression levels. Recently, these drawbacks have begun to be overcome by the use of specialty carriers such as polylysine, liposomes, or polyethyleneimines, and by inclusion of suitable DNA elements to enhance gene expression and longevity. Recent advancements in the field have yielded non-viral vectors that have favorable safety profiles, lack immunogenicity, exhibit long-term elevated gene expression, and show efficient transfection in the retina and RPE, making them poised to transition to clinical applications. Here we discuss the advancements in nanotechnology and vector engineering that have improved the prospects for clinical application of non-viral gene therapy in the RPE.
近年来，眼基因治疗作为一种靶向角膜、视网膜和视网膜色素上皮（RPE）疾病的治疗方法得到了广泛的探索。腺相关病毒（AAV）介导的基因治疗在几项 RPE 临床试验中显示出了前景，但 AAV 的载物能力有限，且具有潜在的免疫原性。然而，传统上，非病毒替代物一直受到转染效率低、短期表达和低表达水平的困扰。最近，通过使用多聚赖氨酸、脂质体或聚乙烯亚胺等专业载体，并包含合适的 DNA 元件来增强基因表达和持久性，这些缺点开始得到克服。该领域的最新进展产生了非病毒载体，这些载体具有良好的安全性、无免疫原性、表现出长期的高基因表达，并且在视网膜和 RPE 中具有高效的转染效率，使其有望过渡到临床应用。在这里，我们讨论了纳米技术和载体工程的进展，这些进展提高了非病毒基因治疗在 RPE 中临床应用的前景。
