EGFR Gene Editing

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EGFR Gene Editing    

Epidermal Growth Factor Receptor (EGFR) is a transmembrane glycoprotein with molecular weights ranging from 170 to 185 KDa, expressed in some normal epithelial, mesenchymal, and neurogenic tissue. And EFGR is one of the four members of the ErbB family tyrosine kinase receptors. It consists of a C-terminus intracellular region that possesses the kinase activity, and an N-terminus extracellular ligand-binding site, a hydrophobic transmembrane domain. Activation of EGFR initiates a cascade of downstream signaling pathways, including the KRAS-BRAF-MEK-ERK pathway, PI3K/Akt, and signal transducer and activator of transcription (STAT) factors, to regulate gene expression, proliferation, angiogenesis, apoptosis inhibition, cell motility, metastasis, adhesion, and angiogenesis. Anyway, the final result is cell proliferation or cell maintenance by inhibition of apoptosis (Figure 1).

 Epidermal growth factor receptor downstream signaling pathwaysFigure 1. Epidermal growth factor receptor downstream signaling pathways (Mary Jue Xu, 2017)

EGFR Targeted Therapies

EGFR is a recognized regulator of the oncogenic phenotype. Overexpression of EGFR has been reported and implicated in the pathogenesis of many human malignancies including lung cancer, head and neck, bladder cancer, ovarian cancer, and cervical cancer. Some studies have reported that EGFR overexpression is associated with advanced disease, poor chemosensitivity, and prognosis. In view of the functional involvement of EGFR in a variety of cellular processes, several approaches targeting and interfering with EGFR-mediated have been developed. There are currently two different approaches, one is monoclonal antibodies, and the other is small molecule tyrosine kinase inhibitors (Table 1). The cross-talk between members of the EGFR family and other signaling pathways can easily lead to treatment resistance, which remains a major obstacle. And researches on the relation between EFGR and pathogenesis of cancer and the studies of EFGR-targeted cancer treatment are still need to be further developed.

Table1. EGFR Targeted Therapies

CompoundDescription
EGFR-targeted Monoclonal Antibodies
Cetuximab Erbitux (IMC-C225)Chimeric, murine antibody and human IgG1
Panitumumab Vectibix (ABX-EGF)Humanized mAb
NimotuzumabHumanized mAb
Zalutumumab GenmabHuman IgG1
DuligotuzumabHumanized dual EGFR/HER3 mAb
EGFR-targeted Tyrosine Kinase Inhibitors
Gefitinib Iressa (ZD1839)Reversible binding EGFR specific Oral medicine
Erlotinib Tarceva (OSI-774)Reversible binding EGFR specific
Lapatinib TykerbReversible binding Inhibition of HER2/neu and EGFR
AfatinibIrreversible Pan-ErbB binding
Dasatinib (Sprycel)c-Scr kinases; thought to interfere with nuclear localization and of EGFR
DacomitinibIrreversible Pan-ErbB binding
ASP8273Irreversible binding Affinity higher for EGFR activating and T790M mutations compared to wild type

EGFR Gene Editing Service

Using genome editing technology, we can edit EGFR gene in a short time to better study the role of EFGR in tumorigenesis and tumor treatment. CRISPR/Cas9 PlatformCB at Creative Biogene can provide you custom EGFR knock-out or knock-in cell and animal model services to meet your specific project needs and provide experienced scientific support at every step.

  • EFGR Gene Editing Cell Line Generation

CRISPR/Cas9 PlatformCB has rich experience in EGFR gene editing service for various cell lines, including easy-to-transfect cell lines and hard-to-transfect cells. Our full cell line generation service cover from sgRNA design/construction to final cell line generation/verification. Our expert staff has succeeded in dozens of EGFR knockout cell line generation projects. In addition, we also provide one stop custom EGFR knock-in cell line generation service, including point mutation and gene insertion. Our EGFR 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
✧ Validate the knockout/knockin/point mutation of EFGR by PCR and sequencing
✧ Produce cryogenic preserved vials of stable cells and a final report

Alternative host cell line: CHO, HEK293, HEK239T, Hela, MDA-MB-453, MDA-MB-231NIH3T3, T47D, Neuro2a, HepG2, MCF7, RKO, K562, RAW264.7, et al.

  • EFGR Gene Editing Animal Model Generation

CRISPR/Cas9 PlatformCB has extensive experience in manipulating animal embryos and been very successful in incorporating CRISPR-Cas9 technology into our program, which has been well recognized by our customers. Based on our research platform and team of scientists, we can produce EGFR transgenic and gene-targeted animals at a reasonable cost in a shorter time. Our EGFR gene editing animal model generation services include:

➢ EFGR gene conventional knockout animals
➢ EFGR gene conditional knockout animals
➢ EFGR point mutation animals
➢ EFGR knockin animals

Alternative species: mouse, rat, rabbit, zebrafish, C.elegans, etc.

As one of the leading-edge experts among the frontier of CRISPR-CAS9 genome editing technology, CRISPR/Cas9 PlatformCB is professional in providing custom genome engineering projects. Based on national advanced laboratory platforms, professional team and efficient operation, we guarantee our clients the most reliable and efficient research services to best match your research goals. If you don't see the gene editing service related to EGFR you need above, don't hesitate to contact us.

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References:

  1. Yoshida T etc. Targeting epidermal growth factor receptor: central signaling kinase in lung cancer. Biochemical pharmacology. 2010;80:613–623.
  2. Sun M etc. HER family receptor abnormalities in lung cancer brain metastases and corresponding primary tumors. Clinical cancer research. 2009;15:4829–4837.
  3. Mary Jue Xu etc. EGFR-Targeted Therapies in the Post-Genomic Era. Cancer Metastasis Rev. 2017 Sep; 36(3): 463–473.
  4. Sara Sigismund etc. Emerging functions of the EGFR in cancer. Mol Oncol. 2018 Jan; 12(1): 3–20.
  5. Gillian Bethune etc. Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis. 2010 Mar; 2(1): 48–51.
  6. Parthasarathy Seshacharyulu etc. Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets. 2012 Jan; 16(1): 15–31.
For research use only. Not intended for any clinical use.

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