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CCR5 (C-C chemokine receptor type 5), known as CD195, is a protein on the surface of white blood cells, also a seven transmembrane G-protein–coupled receptor, which is involved in the immune system. The CCR5 protein belongs to the β chemokine receptors family of IMPs (integral membrane proteins), Cognate ligands of CCR5 include CCL3, CCL4, and CCL3L1. CCR5 also interacts with CCL5, which is known as RANTES, a chemotactic cytokine protein. CCR5 activation of Ca2+ signaling and cellular migration is preserved in immune cells and cancer cells. Other pathways induced by CCR5, include the PI-3'K pathway, PDK1 and the serine/threonine kinase protein kinase B (AKT), which in turn induces glycolysis, cell survival and proliferation, growth and proliferation of progenitor and stem cells, immune cell differentiation, and the release of eIF4E to promote cap-dependent translation, which are shown below. (Figure 1).
Figure 1. CCR5 signaling in immune and cancer cells (Xuanmao Jiao, etc. 2019)
CCR5 and Diseases
CCR5 is predominantly expressed on T cells, macrophages, dendritic cells, eosinophils, microglia and a subpopulation of either breast or prostate cancer cells, and besides overexpressed in gastric adenocarcinoma and gastric cancer, colorectal carcinoma, melanoma, Hodgkin lymphoma, pancreatic cancer, head and neck cancer, esophageal cancer, acute lymphocytic leukemia, and other tumors. CCR5 is an essential co-receptor for HIV, and has been strongly implicated in cancers listed above, in precancerous diseases [nonalcoholic steatohepatitis (NASH)], and cancer therapy–related disease (bone marrow transplant–related GvHD).
Preclinical and Clinical Studies Targeting CCR5
Preclinical and clilnical evaluations of antagonists targeting CCR5, like small-molecule antagonist, maraviroc and vicriviroc, or leronlimab, which blocked metastasis of human breast cancer xenografts (MDA-MB-231 cells) in immunodeficient mice via the inhibition of homing, and enhanced cell killing by DNA-damaging chemotherapeutic agents, were performed, including studies of ligand binding and chemotaxis. In mice, an anti-CCR5 antibody inhibited B16 melanoma growth and MDSC accumulation in tumor tissues. Three clinical studies targeting CCR5 for metastatic cancer have been approved by the FDA. Each study combines a drug and a biologic for CCR5+ metastatic cancer.
CCR5 Gene Editing Service
CRISPR/Cas9 PlatformCB, a global leading biotechnological company specializing in gene editing, is dedicated to offering comprehensive CRISPR/Cas9 gene editing services and products for academic research, biotech research and pharmaceutical drug discovery. With deep gene editing knowledge and extensive experience in experimental operation and data processing, we help you effectively control target genes knockout/knockin/point mutation in cells or animals via CRISPR/Cas9 technology.
Based on our platform, CRISPR/Cas9 PlatformCB has successfully implemented gene editing of CCR5 in a variety of cell lines, including easy-to-transfect cell lines and hard-to-transfect cells. Our full cell line generation services cover from sgRNA design/construction to final cell line generation/verification. We also provide you with one-stop services for custom CCR5 gene editing cell line you desire generation service, including point mutation and gene insertion, conditional knock-out/knock-in. Our CCR5 gene editing cell line generation services include:
➢ SgRNA design and synthesis
➢ Transfect the cell line you interest
➢ Select the high expression cell and sort monoclonal cell
Host cell line: HEK293, CHO, Chem-1, CHO-K1/Gα15, etc. Other host cell lines can be also available according to your requirements.
As CRISPR enabled targeted genome editing in a simple, efficient, and economical manner, the process of creating transgenic animals has become more and more simpler. CRISPR/Cas9 CRISPR/Cas9 PlatformCB has extensive experience in manipulating animal embryos and been very successful in incorporating CRISPR-Cas9 technology into our program, which have been well recognized by our customers. Based on our research platform and team of scientists, we can produce CCR5 transgenic and gene-targeted animals at a reasonable cost in a shorter time. Our CCR5 gene editing animal model generation services include:
➢ CCR5 gene conventional knockout animals
➢ CCR5 gene conditional knockout animals
➢ CCR5 point mutation animals
➢ CCR5 knockin animals
Alternative species: mouse, rat, rabbit, zebrafish, C. elegans, etc.
CRISPR/Cas9 PlatformCB is devoted to providing the best gene editing services to accelerate the achievement of your research goals. With skilled and experienced genomics experts, we are able to provide our clients with professional and efficient custom CRISPR/Cas9 services to meet your special requirements. We are committed to providing the most reliable and effective research services and products to best meet your research goals with excellent quality management and quality assurance capacity. If you have any questions, please feel free to contact us.
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