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脂质纳米粒子介导的mRNA输送到老鼠和人类视网膜和其他眼睛组织中

Cheri Z Chambers¹, Gillian L Soo¹, Abbi L Engel¹

¹Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, USA.

Translational vision science & technology

|July 9, 2024

概括

脂质纳米颗粒有效地在小鼠和人眼组织 (包括视网膜) 中传递mRNA用于基因表达. 这种非病毒性方法对未来的眼部基因疗法显示出有前途,没有显著的炎症.

科学领域:

眼科医生眼科眼科
基因治疗基因治疗
纳米医学是一种纳米医学.

背景情况:

脂质纳米颗粒 (LNP) 提供了一种有前途的非病毒方法,用于将mRNA输送到眼部组织.
眼睛中的基因疗法旨在在特定细胞类型中表达治疗性蛋白质.
腺相关病毒 (AAV) 载体是常用的,但非病毒方法正在作为替代品被探索.

研究的目的:

评估包装在LNP中的mRNA在驱动小鼠和人类眼组织中的基因表达中的有效性.
评估LNP输送后视网膜细胞中基因表达的特异性.
调查LNP作为眼部应用的非病毒基因传递系统的潜力.

主要方法:

携带mRNA的LNP通过静脉内注射被引入小鼠的眼睛.
人类视网膜色素表皮质 (RPE) 和视网膜扩增剂被用于评估人类组织中的基因表达.
组织学,免疫光学和成像学被用来分析表达特异性.

主要成果:

在小鼠中,编码GFP和状神经变因子 (CNTF) 的mRNA被Müller glia和RPE特异地表达.
在注射后6小时的小鼠中没有观察到急性炎症变化.
人类RPE表达了高水平的GFP,而人类视网膜扩展体显示了Müller状细胞和巨细胞中的GFP表达.

结论:

视网膜细胞亚群的可靠传染被证明是体内 (老鼠) 和体外 (人) 眼组织.
对于小鼠的RPE转染,静脉内注射足够.
这项研究代表了使用LNP在人眼组织中进行mRNA输送的首次演示.

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