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首页> 外文期刊>Nucleic Acid Therapeutics >Delivery of Antisense Oligonucleotides to the Cornea
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Delivery of Antisense Oligonucleotides to the Cornea

机译：向角膜递送反义寡核苷酸

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摘要

Antisense oligonucleotides (ASOs) are synthetic nucleic acids that recognize complementary RNA sequences inside cells and modulate gene expression. In this study, we explore the feasibility of ASO delivery to the cornea. We used quantitative polymerase chain reaction to test the efficacy of a benchmark ASO targeting a noncoding nuclear RNA, Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), in a human corneal endothelial cell line, ex vivo human corneas, and in vivo in mice. In vivo delivery was via intravitreal or intracameral injections as well as topical administration. The anti-MALAT1 ASO significantly reduced expression of MALAT1 in a corneal endothelial cell line. We achieved a dose-dependent reduction of target gene expression in endothelial tissue from ex vivo human donor corneas. In vivo mouse experiments confirmed MALAT1 reduction in whole corneal tissue via intravitreal and intracameral routes, 82% and 71% knockdown, respectively (P < 0.001). Effects persisted up to at least 21 days, 32% (P < 0.05) and 43% (P < 0.05) knockdown, respectively. We developed protocols for the isolation and analysis of mouse corneal endothelium and observed reduction in MALAT1 expression upon both intravitreal and intracameral administrations, 64% (P < 0.05) and 63% (P < 0.05) knockdown, respectively. These data open the possibility of using ASOs to treat corneal disease.
机译：反义寡核苷酸（ASOS）是合成核酸，其识别细胞内的互补RNA序列并调节基因表达。在这项研究中，我们探讨了ASO交付到角膜的可行性。我们使用定量聚合酶链反应以测试基准ASO的疗效靶向非分量核RNA，转移相关的肺腺癌转录1（MALAT1），在人角膜内皮细胞系，例如小鼠体内。体内递送通过玻璃体玻璃体或肠溶内注射以及局部给药。抗马拉特1 aso在角膜内皮细胞系中显着降低了Malat1的表达。我们依赖于来自例如人体供体角膜的内皮组织中靶基因表达的剂量依赖性降低。在体内小鼠实验中，通过玻璃体内和颈内途径，82％和71％敲低，确认了MALAT1整体角膜组织的减少（P <0.001）。效果持续至少21天，32％（P <0.05）和43％（P <0.05）敲低。我们开发了小鼠角膜内皮分离和分析的协议，并观察到玻璃体内和颈内给药后的Malat1表达，64％（P <0.05）和63％（P <0.05）敲低。这些数据打开了使用ASO治疗角膜疾病的可能性。

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