Lim Yeongseo, Campochiaro Peter A, Green Jordan J
From the Department of Biomedical Engineering (Y.L., J.J.G.), Johns Hopkins University, Baltimore, Maryland, USA; Translational Tissue Engineering Center (Y.L., J.J.G.), Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Johns Hopkins Translational ImmunoEngineering Center (Y.L., J.J.G.), Johns Hopkins University, Baltimore, Maryland, USA.
Department of Ophthalmology (P.A.C., J.J.G.), Johns Hopkins University, Baltimore, Maryland, USA; Department of Neuroscience (P.A.C.), Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Am J Ophthalmol. 2024 Dec 21. doi: 10.1016/j.ajo.2024.12.010.
Current treatments for retinal and choroidal neovascular diseases suffer from insufficient durability, including anti-vascular endothelial growth factor-A agents. It is, therefore, of interest to explore alternative methods that could allow for robust improvement in visual acuity with fewer injections required.
Literature review.
Among various preclinical and clinical studies in the literature, a promising approach is the use of suprachoroidal injection with viral and nonviral gene delivery vectors. Compared with other ocular injection methods, suprachoroidal injection has demonstrated wide biodistribution of injected agents and safety as an outpatient procedure. In terms of viral vectors, suprachoroidal injection of an adeno-associated virus 8 vector expressing an anti-vascular endothelial growth factor-A antibody fragment has shown an excellent safety profile and evidence of biological activity. In terms of nonviral vectors, lipid nanoparticles and polymeric nanoparticles both demonstrate strong promise for ocular gene therapy in large animal models. In particular, biodegradable poly(β-amino ester) nanoparticles show excellent biodistribution, safety, and efficacy for gene therapy via the suprachoroidal route. Nonviral nanoparticle approaches can have notable advantages over viral vectors in terms of carrying capacity, redosability, and manufacturing costs. An advantage of gene therapy is that once a delivery vector has been optimized, genetic cargos can be readily tailored without changing the safety, efficacy, and pharmacokinetic properties of the delivery vector.
This review highlights recent progress that has been made and compares viral and nonviral suprachoroidal gene delivery for the treatment of retinal and choroidal vascular diseases. Suprachoroidal gene therapy is an emerging biotechnology that holds substantial potential to make a translational impact in treating these diseases.
包括抗血管内皮生长因子-A制剂在内的目前用于视网膜和脉络膜新生血管疾病的治疗方法，其耐久性不足。因此，探索能够在减少注射次数的情况下显著提高视力的替代方法具有重要意义。
文献综述。
在文献中的各种临床前和临床研究中，一种有前景的方法是使用病毒和非病毒基因递送载体进行脉络膜上腔注射。与其他眼部注射方法相比，脉络膜上腔注射已证明注射剂具有广泛的生物分布，并且作为门诊手术具有安全性。就病毒载体而言，脉络膜上腔注射表达抗血管内皮生长因子-A抗体片段的腺相关病毒8载体已显示出良好的安全性和生物活性证据。就非病毒载体而言，脂质纳米颗粒和聚合物纳米颗粒在大型动物模型的眼部基因治疗中均显示出巨大潜力。特别是，可生物降解的聚（β-氨基酯）纳米颗粒通过脉络膜上腔途径进行基因治疗时，显示出优异的生物分布、安全性和疗效。非病毒纳米颗粒方法在携带能力、可重复给药性和制造成本方面比病毒载体具有显著优势。基因治疗的一个优点是，一旦递送载体得到优化，遗传载荷可以很容易地进行调整，而不会改变递送载体的安全性、疗效和药代动力学特性。
本综述强调了最近取得的进展，并比较了用于治疗视网膜和脉络膜血管疾病的病毒和非病毒脉络膜上腔基因递送。脉络膜上腔基因治疗是一种新兴的生物技术，在治疗这些疾病方面具有产生转化影响的巨大潜力。
