Tolerability and tropism of recombinant adeno-associated virus vectors in the African green monkey (Chlorocebus sabaeus) anterior chamber

IF 4.6 3区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Gene Therapy Pub Date : 2023-05-24 DOI:10.1038/s41434-023-00407-z

Kristina J. Chern, Kimicia Z. Issac, Zendorf D. Gumbs, Merissa E. O’Connor, Matthew S. Lawrence, Daniel M. Lipinski

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Abstract

While many studies have investigated the use of recombinant adeno-associated vectors (rAAV) in the posterior chamber for treatment of inherited retinal diseases, fewer studies have looked at rAAV’s ability to transduce cells within the anterior chamber. This study focuses on evaluating the tropism and tolerability of three rAAV serotypes—rAAV2/6, rAAV2/9, and rAAV2/2[MAX]—expressing a green fluorescent protein (GFP) reporter following intracameral injection in the non-human primate (NHP) African green monkey (Chlorocebus sabaeus) model. Injection of high dose (1 × 1012 vg/eye) rAAV vector resulted in transient inflammation characterized by aqueous flare and cellular infiltrate that resolved without intervention in all serotypes. Post-mortem histology revealed widespread expression of GFP in cells of the trabecular meshwork and iris in high dose rAAV2/6, rAAV2/9, and particularly rAAV2/2[MAX] eyes, indicating that rAAV vectors of these serotypes have broad tropism for cells of the anterior chamber and may facilitate the treatment of blinding disorders, such as glaucoma.

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重组腺相关病毒载体在非洲绿猴（Chlorocebus sabaeus）前房中的耐受性和嗜性。

虽然许多研究已经调查了在前房中使用重组腺相关载体（rAAV）治疗遗传性视网膜疾病，但很少有研究关注rAAV在前房内转导细胞的能力。本研究的重点是评估在非人灵长类动物（NHP）非洲绿猴（Chlorocebus sabaeus）模型中进行体腔内注射后，表达绿色荧光蛋白（GFP）报告基因的三种rAAV血清型rAAV2/6、rAAV2/9和rAAV2/2[MAX]的向性和耐受性。注射高剂量（1 × 1012 vg/眼）rAAV载体导致以水性闪光和细胞浸润为特征的短暂炎症，其在不干预所有血清型的情况下解决。尸检组织学显示，在高剂量rAAV2/6、rAAV2/9，特别是rAAV2/2[MAX]眼中，GFP在小梁网和虹膜细胞中广泛表达，表明这些血清型的rAAV载体对前房细胞具有广泛的嗜性，并可能有助于治疗致盲性疾病，如青光眼。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Gene Therapy 医学-生化与分子生物学

CiteScore

9.70

自引率

2.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Gene Therapy covers both the research and clinical applications of novel therapeutic techniques based on a genetic component. Over the last few decades, significant advances in technologies ranging from identifying novel genetic targets that cause disease through to clinical studies, which show therapeutic benefit, have elevated this multidisciplinary field to the forefront of modern medicine.

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