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人类和小鼠的长非编码RNA被重新设计为外源传递,可以减少人类巨细胞和小鼠中的LPS诱导的炎症

Janice Pang¹, Yan Ming Anson Lau¹, Fabiha Mahbub¹

¹Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.

Science signaling

|March 10, 2026

概括

研究人员设计了长非编码RNA (lncRNAs) 来治疗炎症. 这种新的方法成功地减少了小鼠和人类细胞的炎症反应,显示了新的疾病治疗的潜力.

科学领域:

分子生物学分子生物学
免疫学免疫学免疫学
在RNA治疗方面,RNA疗法.

背景情况:

长非编码RNAs (lncRNAs) 是基因表达的关键调节者,影响细胞和系统功能.
lncRNA在正常生理学和疾病发病过程中都起着至关重要的作用.
开发基于lncRNAs的治疗策略对治疗各种疾病具有重大前景.

研究的目的:

建立和优化工程 lncRNAs 的使用,作为治疗急性炎症的治疗方式.
在临床前模型中研究重新设计的 lncRNAs (GAPLINC,MIST,DRAIR) 在降低炎症反应方面的有效性.
为了证明基于 lncRNA 的疗法在人类细胞中的潜在临床适用性.

主要方法:

已建立了三种特定的lncRNAs的体外转录合成和HPLC净化工作流.
优化 lncRNA 异型, 5' cap,3' poly(A) 尾,以及化学基因修改,以提高特异性和性能.
开发并优化了脂质纳米粒子系统,以在体内有效地传递 lncRNA,而不会产生混效应.

主要成果:

工程 lncRNAs (GAPLINC,MIST,DRAIR) 在小鼠巨和体内显著降低了脂多糖 (LPS) 诱导的炎症.
GAPLINC和DRAIR分别降低了IL-1β和IL-6的转录.
在转录后,MIST减弱了TNFα的产生,而重新设计的GAPLINC在人类单细胞中显示出有效性.

结论:

该研究成功地建立了一种基于核酸的新型治疗模式,使用工程 lncRNAs.
这些发现表明,重新设计的调节性 lncRNAs 有潜力有效治疗炎症性疾病.
这种方法为开发针对性治疗的一系列疾病提供了一个有希望的新途径.

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相关概念视频

lncRNA - Long Non-coding RNAs

lncRNA - Long Non-coding RNAs

In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...