循环mRNA的高效细胞表达使得蛋白质表达时间延长
Mildred J Unti1, Samie R Jaffrey1
1Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
Cell chemical biology
|October 26, 2023
概括
研究人员开发了一种新方法,用于在细胞内部创建循环信使RNA (mRNA),从而导致更长的蛋白质生产,并改善mRNA疫苗和治疗的治疗潜力.
科学领域:
- 生物技术是生物技术.
- 分子生物学分子生物学
- 在RNA治疗方面,RNA疗法.
背景情况:
- 使者RNA (mRNA) 疗法在细胞中面临快速降解,限制了它们的有效性.
- 循环mRNA提供更长的半衰期,增强蛋白质合成持续时间.
- 目前生产循环mRNA的方法主要是体外的,这给细胞内应用带来了挑战.
研究的目的:
- 为了使旋系统适应循环mRNA的高效细胞内合成.
- 为了确定高循环mRNA和蛋白质表达的最佳促进子和内部核糖体进入部位 (IRES) 组合.
- 为了证明细胞内合成的圆形mRNA在病毒样粒子 (VLP) 疗法中的实用性.
主要方法:
- 适应旋系统 (用于持久过度表达的Twister优化RNA) 系统用于细胞内循环mRNA的生产.
- 选各种促进物和IRES元素以优化循环mRNA合成.
- 将合成的圆形mRNA包装成类似病毒的粒子 (VLP).
主要成果:
- 旋系统成功适应细胞内循环mRNA合成.
- 识别特定的促进剂-IRES组合,产生高水平的循环mRNA和随后的蛋白质表达.
- 证明循环mRNA可以有效地包装到VLPs中,以持续蛋白质表达.
结论:
- 开发的平台使循环mRNA的有效细胞内合成成为可能.
- 与线性mRNA相比,这种方法显著提高了蛋白质表达持续时间.
- 细胞内合成的圆形mRNA有望改善基于VLP的治疗方法.
相关概念视频
02:22Regulated mRNA Transport
6.3K
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
6.3K
01:23Regulation of Expression at Multiple Steps
923
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
923