相关实验视频

Updated: Jul 15, 2025

Using CRISPR/Cas9 to Knock Out GM-CSF in CAR-T Cells

Using CRISPR/Cas9 to Knock Out GM-CSF in CAR-T Cells

Published on: July 22, 2019

在临床CRISPR-Cas9工程T细胞中减轻染色体损失

Connor A Tsuchida¹, Nadav Brandes², Raymund Bueno²

¹University of California, Berkeley-University of California, San Francisco Graduate Program in Bioengineering, University of California, Berkeley, Berkeley, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.

|October 5, 2023

概括

CRISPR-Cas9基因编辑可能导致T细胞的染色体损失,这是治疗的安全问题. 在临床应用中,一种新的制造工艺和p53表达减少了这种基因毒性.

科学领域:

基因组学
细胞生物学
免疫疗法

背景情况:

通过CRISPR-Cas9基因组编辑, 提升了T细胞疗法.
在CRISPR-Cas9应用中,染色体丢失是潜在的安全问题.

研究的目的:

确定Cas9诱导的染色体损失是否广泛.
评估染色体损失的临床相关性.
确定减轻染色体损失的策略.

主要方法:

在人类T细胞中进行系统分析.
排列并将CRISPR屏幕进行聚合.
在临床试验中对修改细胞制造工艺的评估 (NCT03399448).

主要成果:

染色体损失可以在整个基因组中普遍存在,影响向的染色体.
染色体丢失的T细胞在培养中持续存在,这给临床带来了挑战.
一个修改的制造工艺和p53表达显著减少了染色体损失.

结论:

在T细胞工程中,Cas9诱导的染色体损失是显著的基因毒性风险.
修改制造工艺和p53表达提供了减轻这种风险的策略.
这些发现对于CRISPR- Cas9工程T细胞疗法的安全临床应用至关重要.

关键词:

卡尔T细胞在CRISPR屏幕上在CRISPR-Cas9中 DNA 修复一个T细胞没有化染色体损失临床试验基因组编辑免疫工程

更多相关视频

Production of Human CRISPR-Engineered CAR-T Cells

Production of Human CRISPR-Engineered CAR-T Cells

Published on: March 15, 2021

Electroporation-Based CRISPR-Cas9-Mediated Gene Knockout in THP-1 Cells and Single-Cell Clone Isolation

Electroporation-Based CRISPR-Cas9-Mediated Gene Knockout in THP-1 Cells and Single-Cell Clone Isolation

Published on: February 28, 2025

相关概念视频

CRISPR

CRISPR

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...

CRISPR/Cas9 Genome Editing

CRISPR/Cas9 Genome Editing

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...

Homologous Recombination

Homologous Recombination

The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...