定量蛋白质组学和CRISPR/Cas9编辑揭示了UPR介导的控制混合体瘤中的免疫球蛋白平衡
Rubing Zou1, Xinying Lu1, Ying Liu1
1Institute of Pesticide and Environmental Toxicology, Zhejiang Key Laboratory of Biology and Ecological Regulation of Crop Pathogens and Insects, Ministry of Agriculture and Rural Affairs Key Laboratory of Molecular Biology of Crop Pathogens and Insect Pests, Zhejiang University, Hangzhou, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|January 21, 2026
概括
这项研究表明,展开的蛋白质响应 (UPR) 途径对于混合体瘤中的抗体产生至关重要. 一个新的报告系统有效地监测UPR激活,以确保抗体稳定性和质量控制.
科学领域:
- 生物技术是生物技术.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 单克隆抗体在经济上至关重要,但易受免疫球蛋白链损失的影响,破坏稳态.
- 混合瘤中Ig生产的损失会损害它们的识别能力和整体质量控制.
研究的目的:
- 调查展开蛋白质响应 (UPR) 途径在调节免疫球蛋白 (Ig) 链生产中的作用.
- 开发一种新的报告系统,用于实时监测UPR激活和抗体稳定性.
主要方法:
- 利用CRISPR/Cas9进行基因淘汰和救援实验,以UPR途径为目标.
- 使用CRISPR/HDR将mGFP标签插入Hspa5基因以进行实地UPR监测.
- 进行蛋白质组分析和光激活细胞分类,以将UPR活性与Ig生产相关联.
主要成果:
- 确定了Xbp1s,一个UPR转录因子,对于混合瘤抗体的产生至关重要.
- 在UPR激活 (mGFP信号) 和IgG水平之间建立了强烈的负相关性 (R2 = 0.86).
- 证明了报告员系统在识别功能障碍的亚克隆和受损的Ig分泌的有效性.
结论:
- UPR途径在调节Ig合成和维持抗体平衡方面发挥着重要作用.
- 开发的基于UPR的报告员系统为监测生物制药生产中的抗体稳定性提供了宝贵的工具.
相关概念视频
CRISPR/Cas9 Genome Editing
1.8K
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...
1.8K
CRISPR
57.6K
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...
57.6K
CRISPR and crRNAs
18.8K
Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
18.8K
What is Homeostasis?
52.8K
Maintaining homeostasis requires that the body continuously maintain its internal conditions. Each physiological condition has a particular set point, from body temperature to blood pressure to levels of certain nutrients. A set point is the physiological value around which the normal range fluctuates. A normal range is a restricted set of values that is optimally healthful and stable. For example, the set point for normal human body temperature is approximately 37°C (98.6°F).
52.8K
Hybridoma Technology
17.3K
Hybridoma technology is used for the large-scale production of monoclonal antibodies. Monoclonal antibodies bind to only a single antigenic determinant or epitope. Such antibodies are used in research, diagnostics, and disease therapy. The hybridoma technology established in 1975 by Georges Köhler and Cesar Milstein was awarded the Nobel Prize in Medicine in 1984 for revolutionizing research and therapy.
Hybridoma Selection
Commonly used fusion techniques — electroporation,...
Hybridoma Selection
Commonly used fusion techniques — electroporation,...
17.3K
pH Homeostasis
18.3K
Acid-base homeostasis is essential for maintaining normal physiological activities in humans. The pH of various body fluids is strictly regulated because it is critical for the optimal activity of enzymes involved in metabolic reactions. Enzymes are basically proteins, so, any significant change in pH can affect their structure and activity. In humans, pH is regulated using three primary mechanisms— chemical buffer systems, respiratory regulation, and renal regulation.
Respiratory...
Respiratory...
18.3K


