主编媒介的ACE2的功能重塑阻止了多种人类冠状病毒的进入,包括SARS-CoV-2变种
Wenwen Zhao1,2,3, Jifang Li1,2,3, Xiao Wang1,2,4
1Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech University Shanghai China.
MedComm
|September 13, 2023
概括
使用原始编辑编辑ACE2受体的基因编辑提供了针对SARS-CoV-2变种的新策略. 这种方法修改了ACE2以阻止病毒进入,提供了对多种冠状病毒的广泛保护.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 基因编辑 基因编辑
背景情况:
- 在SARS-CoV-2中,尖端蛋白针对ACE2进入细胞.
- 奥米克朗亚型体现出免疫逃避,降低了疫苗的疗效.
- 准宿主ACE2提供了一个更稳定的抗病毒策略.
研究的目的:
- 调查主要编辑修改ACE2以赋予对SARS-CoV-2的抗性.
- 评估ACE2编辑是否可以提供对冠状病毒的广泛保护.
主要方法:
- 利用主要编辑器 (PE) 精确编辑在选定的网站上ACE2基因.
- 评估了ACE2残留物变化对病毒结合和ACE2生理功能的影响.
- 测试了编辑ACE2对伪型SARS-CoV-2变种,SARS-CoV和HCoV-NL63以及活的Delta变种病毒的疗效.
主要成果:
- 特定的ACE2残留修饰 (Q24/D30/K31和/或K353) 消去了病毒结合,同时保留了ACE2功能.
- 通过PE介导的ACE2编辑阻止了SARS-CoV-2变种,SARS-CoV和HCoV-NL63.3的进入.
- 显著抑制了活体SARS-CoV-2Delta变种的复制.
结论:
- 首次编辑ACE2是针对冠状病毒的广泛抗病毒活性的一个有希望的策略.
- 宿主因子的基因编辑为病毒逃脱和抵抗提供了很高的障碍.
- 这种方法有可能控制高风险的传染病.
相关概念视频
RNA Editing
9.0K
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
9.0K
Leaky Scanning
5.2K
During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA. Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.2K
CRISPR/Cas9 Genome Editing
48
The CRISPR-Cas system serves as a bacterial defense mechanism against invading genetic elements such as viruses and plasmids, forming the foundation for its adaptation as a powerful genome-editing tool. Originally discovered in prokaryotes, this system has been repurposed to revolutionize genetic engineering across a wide range of organisms, including plants, animals, and humans. The core component, Cas9, is an endonuclease derived from Streptococcus pyogenes, capable of introducing...
48
Viruses with RNA Genomes
55
RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
55
CRISPR
52.2K
Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...
52.2K


