[JAN Bestselling Products] CRISPR Screens--Metabolic, Kinase, and Drug targets
CRISPR screening is a tool for high-throughput gene function research. A CRISPR library contains a set of pre-designed sgRNA sequences, which can guide the Cas9 protein to cleave the double-stranded DNA, thus knocking out genes. In this article, we recommend the three best-selling CRISPR libraries this month, and introduce corresponding literatures interpretation. Hope this could inspire your research!
Metabolic Gene Knockout Library Reveals Potential Mechanisms of Hepatocellular Carcinoma
CSCs (Cancer stem cells), with their self-renewal and multipotential properties, are thought to be a key factor in cancer onset, progression, and drug resistance, and have been studied in depth, including their characterization, function, and relationship to treatment response.
Researchers used the Human CRISPR Metabolic Gene Knockout library in hepatocellular carcinoma cell tumors and found that SCARB2 gene deletion suppressed the cancer stem cell-like properties of hepatocellular carcinoma cells and attenuated the initiation and progression of hepatocellular carcinoma in MYC (oncogene)-driven and DEN (diethylnitrosamine)-induced hepatocellular carcinoma mouse models. Further studies revealed that the binding of SCARB2 to MYC promotes MYC acetylation, which in turn enhances the transcriptional activity of MYC. Screening of the drug database revealed that polymyxin B, which has a high affinity for the SCARB2 protein, interferes with the SCARB2-MYC interaction and reduces MYC activity. This study identified SCARB2 as a key driver of hepatocellular carcinoma development through CRISPR/Cas9 knockdown library screening, which provides new ideas and potential therapeutic strategies for early diagnosis and treatment of hepatocellular carcinoma.
Fig. 1 CRISPR/Cas9 library screen identifies SCARB2 as key to HCC cell carcinogenesis
Exploring New Pathway of Resistance to a Prostate Cancer Drug by CRISPR Kinase Knockout Library
Prostate cancer (PCa) is the most common non-cutaneous malignancy in male. Enzalutamide (ENZA), a second-generation androgen receptor antagonist, significantly improves overall survival in patients with PCa, but resistance to the drug results in a limited treatment period.
Researchers have identified casein kinase 1α (CK1α) as a therapeutic target for overcoming ENZA resistance through a kinome-wide CRISPR screen. CK1α phosphorylates and regulates the protein abundance of ataxia telangiectasia mutated (ATM). Pharmacological inhibition of CK1α enhances ENZA efficacy of drug-resistant cells and patient-derived xenografts, stabilizes ATM, and restores double-strand break signaling, thereby increasing ENZA-induced cell death and growth arrest. Kinome-wide CRISPR library screening has a key role in the discovery of the CK1α gene in the mechanism of ENZA's pharmacological action, providing important clues and thoughts for prostate cancer therapy.
Fig. 2 A kinome-wide CRISPR screen identifies CK1a as a target for overcoming Enzalutamide resistance in prostate cancer
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and one of the deadliest cancers in the world. Donafenib, a multi-receptor tyrosine kinase inhibitor, is approved for the treatment of patients with advanced HCC, but has been tested to have very limited clinical efficacy, with patients surviving an additional 1.8 months post-treatment, which falls short of clinical expectations.
The researchers found that GSK-J4 and Donafenib are synthetically lethal in hepatocellular carcinoma through the small molecule inhibitor library and the Druggable CRISPR library screening, and validated this synergistic lethality in multiple hepatocellular carcinoma models. It was further found by RNA-seq and ATAC-seq that GSK-J4 synergistically promotes HMOX1 expression with Donafenib, increases intracellular Fe2+ levels, and induce Ferroptosis, and the combination of Donafenib and GSK-J4 was found by cut-target & tag sequencing (CUT&Tag-seq) assay to significantly increase the the frequency of cleavage in the upstream enhancer region of the HMOX1 promoter. Druggable CRISPR library screening identified a new synergistic lethal factor, GSK-J4, which provides a new research idea to improve drug therapy for hepatocellular carcinoma.
Fig. 3 Screening of Druggable CRISPR libraries for Donafenib synergistic lethal effectors
EDITGENE offers aforementioned Metabolic, Kinase, Druggable CRISPR libraries. Pre-made libraries deliver in 1 week, only $1600 get 100ug plasmid library. Explore our CRISPR libraries now>>
Recent Posts
[Research Frontier] New trends in CRISPR-- KO Cells Reveal Key Factors in Ferroptosis
CRISPR screen decodes stimulatory responses of primary T cells
New trends in CRISPR detection: Monkeypox virus detection