对于强化Cas9核蛋白输送的两性性异质的化学演变
Yi Lin1, Xianjin Luo1, Tobias Burghardt1
1Pharmaceutical Biotechnology, Center for Nanoscience, LMU Munich, Butenandtstr. 5-13, 81377 Munich, Germany.
Journal of the American Chemical Society
|July 3, 2023
概括
研究人员开发了新的人工,以有效地进行CRISPR/Cas9基因组编辑. 这些新型载体显著增强基因淘汰和修复,提供了一个有前途的非病毒纳米载体平台.
科学领域:
- 生物技术
- 分子生物学
- 化学生物学
背景情况:
- 在基因组编辑过程中,CRISPR/Cas9核蛋白 (RNP) 传递至关重要.
- 对Cas9 RNP的高效和强大的非病毒载体有很高的需求.
研究的目的:
- 开发新型的人工,以有效地传递Cas9 RNP.
- 为优化非病毒纳米载体建立结构-活性关系.
主要方法:
- 用新型可电离氨基酸设计和合成人造.
- 的疏水性能的系统变化 (logD7.4).
- 对基因组编辑效率的评估 (eGFP淘汰,同质导向修复).
- 对内细胞突变途径和载体稳定性的机制研究.
主要成果:
- 在1nM的RNP剂量下,优化的两异型达到了~88%的eGFP淘汰效果.
- 在报告细胞中达到高达40%的同质导向修复 (HDR).
- 疏水平衡的对离子应激和解离的抵抗性增加.
- 可以通过克拉和宏皮诺细胞介导途径促进内细胞分裂.
结论:
- 开发了一种多功能和可调节的载体平台,用于Cas9 RNP的输送.
- 结构-活性关系为设计有效的非病毒纳米载体提供了化学指南.
- 这些发现通过改进的传递系统推动了基因组编辑技术领域的发展.
相关概念视频
CRISPR/Cas9 Genome Editing
73
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...
73
CRISPR
52.4K
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...
52.4K
Conservative Site-specific Recombination and Phase Variation
6.0K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.0K
Caspases
12.6K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
12.6K


