A non-rational approach to optimized targeting of CRISPR-Cas9 complexes [0.03%]
一种针对CRISPR-Cas9复合物优化靶向的非理性方法
Brandon Wilbanks,Keenan Pearson,L James Maher rd
Brandon Wilbanks
In this issue of Cell Chemical Biology, Bush et al.1 report an in vitro selection method for optimizing CRISPR-Cas9 single-guide RNAs. This approach may be useful in targeting previously intractable genomic sequences. The results also provi...
Identification of KLHDC2 as an efficient proximity-induced degrader of K-RAS, STK33, β-catenin, and FoxP3 [0.03%]
KLHDC2的鉴定及其作为高效邻近诱导降解剂以靶向K-RAS、STK33、β-连环蛋白和FoxP3的功能研究
Sascha Röth,Nur Mehpare Kocaturk,Preethi S Sathyamurthi et al.
Sascha Röth et al.
Targeted protein degradation (TPD), induced by enforcing target proximity to an E3 ubiquitin ligase using small molecules has become an important drug discovery approach for targeting previously undruggable disease-causing proteins. However...
Multimodal, broadly neutralizing antibodies against SARS-CoV-2 identified by high-throughput native pairing of BCRs from bulk B cells [0.03%]
通过高通量原位配对方法从大量B细胞中鉴定出针对SARS-CoV-2的广谱中和抗体
Gladys J Keitany,Benjamin E R Rubin,Meghan E Garrett et al.
Gladys J Keitany et al.
TruAB Discovery is an approach that integrates cellular immunology, high-throughput immunosequencing, bioinformatics, and computational biology in order to discover naturally occurring human antibodies for prophylactic or therapeutic use. W...
HDAC3 and HDAC8 PROTAC dual degrader reveals roles of histone acetylation in gene regulation [0.03%]
HDAC3和HDAC8双降解剂PROTAC揭示组蛋白乙酰化在基因调控中的作用
Yufeng Xiao,Seth Hale,Nikee Awasthee et al.
Yufeng Xiao et al.
HDAC3 and HDAC8 have critical biological functions and represent highly sought-after therapeutic targets. Because histone deacetylases (HDACs) have a very conserved catalytic domain, developing isozyme-selective inhibitors remains challengi...
Mitochondria-targeted melatonin photorelease supports the presence of melatonin MT1 receptors in mitochondria inhibiting respiration [0.03%]
线粒体靶向的褪黑素光释放支持线粒体中存在抑制呼吸的褪黑激素MT1受体
Gloria Somalo-Barranco,Antonio C Pagano Zottola,Abdulrasheed O Abdulrahman et al.
Gloria Somalo-Barranco et al.
The presence of signaling-competent G protein-coupled receptors in intracellular compartments is increasingly recognized. Recently, the presence of Gi/o protein-coupled melatonin MT1 receptors in mitochondria has been revealed, in addition ...
Younghoon Kim,Pooreum Seo,Eunhye Jeon et al.
Younghoon Kim et al.
Chemically induced protein degradation is a powerful strategy for perturbing cellular biochemistry. The predominant mechanism of action for protein degrader drugs involves an induced proximity between the cellular ubiquitin-conjugation mach...
Genetic activation of glycolysis in osteoblasts preserves bone mass in type I diabetes [0.03%]
骨形成细胞遗传性活化糖酵解可防止1型糖尿病引起的骨量丢失
Xing Ji,Rebecca Seeley,Ke Li et al.
Xing Ji et al.
Type I diabetes (T1D) impairs bone accrual in patients, but the mechanism is unclear. Here in a murine monogenic model for T1D, we demonstrate that diabetes suppresses bone formation resulting in a rapid loss of both cortical and trabecular...
Discovery of a highly potent, selective, orally bioavailable inhibitor of KAT6A/B histone acetyltransferases with efficacy against KAT6A-high ER+ breast cancer [0.03%]
KAT6A/B组蛋白乙酰转移酶强效、选择性、口服生物利用的小分子抑制剂的发现及其对KAT6A高表达的ER+乳腺癌的有效性研究
Shikhar Sharma,Chi-Yeh Chung,Sean Uryu et al.
Shikhar Sharma et al.
KAT6A, and its paralog KAT6B, are histone lysine acetyltransferases (HAT) that acetylate histone H3K23 and exert an oncogenic role in several tumor types including breast cancer where KAT6A is frequently amplified/overexpressed. However, ph...
Genetically incorporated crosslinkers identify regulators of membrane protein PD-L1 in mammalian cells [0.03%]
基因交联剂识别哺乳动物细胞中膜蛋白PD-L1的作用调节者
Fangni Chai,Pan Li,Yong He et al.
Fangni Chai et al.
Profiling membrane proteins' interacting networks is crucial for understanding their regulatory mechanisms and functional characteristics, but it remains a challenging task. Here, by combining genetic incorporation of crosslinkers, tandem d...
Arabinose- and xylose-modified analogs of 2',3'-cGAMP act as STING agonists [0.03%]
阿拉伯糖和木糖修饰的2',3'-cGAMP类似物可作为STING激动剂
Wei Xie,Lodoe Lama,Xuejing Yang et al.
Wei Xie et al.
Stimulator of interferon genes (STING) agonists are promising candidates for vaccine adjuvants and antitumor immune stimulants. The most potent natural agonist of STING, 2',3'-cyclic GMP-AMP (2',3'-cGAMP), is subject to nuclease-mediated in...