释放mRNA的持续治疗疗效
Dinglingge Cao1, Meng Tian1, Zhengwei Liu1
1Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
概括
新的策略正在通过改进脂质纳米粒子 (LNP) 输送系统来增强信使RNA (mRNA) 疗法. 这项研究的重点是扩大蛋白质生产,以获得更有效和持续的mRNA治疗.
科学领域:
- 生物技术是生物技术.
- 分子医学是分子医学.
- 药物输送系统 药物输送系统
背景情况:
- 使者RNA (mRNA) 疗法显示出很大的希望,由脂质纳米粒子 (LNP) -mRNA疫苗的成功推动.
- 持续的蛋白质生产对于扩大mRNA治疗应用至关重要.
- 目前的mRNA疗法与RNA不稳定性和低表达效率作斗争,需要频繁的剂量.
研究的目的:
- 审查最近在延长LNP-mRNA系统的治疗疗效方面的进展.
- 探索延长蛋白质翻译持续时间的策略.
- 引导开发优化的LNP-mRNA输送平台.
主要方法:
- 专注于临床前和新兴的NLP-mRNA治疗方法.
- 工程的mRNA分子和LNP输送系统.
- 分析增强持续蛋白质表达的策略.
主要成果:
- 最近的进展集中在工程mRNA和LNP组件上.
- 策略旨在克服固有的RNA不稳定性并提高表达效率.
- 临床前数据表明,治疗效果可能会延长.
结论:
- 延长蛋白质翻译是释放mRNA疗法的全部潜力的关键.
- 优化mRNA和LNP组件对于持续的疗效至关重要.
- 对于先进的LNP-mRNA疗法,需要进一步开发交付平台.
相关概念视频
02:31Nuclear Export of mRNA
7.5K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.5K
02:51mRNA Stability and Gene Expression
5.5K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
5.5K
01:53RNA Stability
33.1K
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
33.1K
02:27Nonsense-mediated mRNA Decay
10.4K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.4K
01:22MicroRNAs
2.9K
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
2.9K