PRAME Gene Editing    

PRAME (preferentially expressed antigen in melanoma; a.k.a. CT130, MAPE, OIP4) was identified as a gene encoding an HLA-A24-restricted peptide, which can stimulate tumor-specific cytotoxic T lymphocytes in a human melanoma cell line. PRAME is located on chromosome 22q11.22 and encodes a 509 amino acid protein.

PRAME is an autosomal cancer-testis antigen (CTA) gene based on its chromosomal location, expression profile and immunogenicity. A study by Lezcano et al, focused on expression of PRAME in cutaneous melanocytic lesions suggested that immunohistochemical analysis of PRAME expression may be useful for diagnostic purposes to support a suspected diagnosis of cutaneous melanoma. PRAME is not only expressed in cutaneous melanoma, but also ocular melanoma and various nonmelanocytic malignant neoplasms, including breast carcinoma, renal cell carcinoma, non-small cell lung cancer, ovarian carcinoma, synovial sarcoma, leukemia, and myxoid liposarcoma. Due to its relatively selective expression in cancer, it is a potential target for cancer treatment. Similar to other CTAs, PRAME has been reported to be epigenetically regulated by DNA methylation. Promoter hypomethylation of PRAME was reported in MDS and AML. Besides, the DNA methyltransferase inhibitor (DNMTi) 5-aza-2′-deoxycytidine (decitabine) induced PRAME expression in cancer cell lines. Importantly, decitabine can also stimulate PRAME-specific immune-reactivity, which indicates an approach to augment PRAME immunotherapy, similar to the strategy for the X-linked CTA NY-ESO-1.

PRAME has been widely investigated as a target for immunotherapy. PRAME tumor expression has been proved to elicit spontaneous humoral and cellular immune responses, and PRAME-based vaccines and adoptive T cell therapies have shown a good safety profile and effectiveness in inducing potent immune responses in tumors. Although the success rate of immunotherapy varies across tumor types and is, in part, impacted by the inherent ability of cancer cells in shaping an immunosuppressive tumor microenvironment. Interestingly, PRAME expression in dedifferentiated liposarcoma and leiomyosarcoma tumors was found to be associated with reduced expression of antigen presentation molecules, a common mechanism of immune escape. Further evidence shows that PRAME could be implicated in the regulation of the immune response. For example, PRAME has been reported to contain 21.8% (iso) leucine residues, and as such likely behaves as a leucine rich repeat (LRR) family protein, sharing structural similarities with Toll-like receptors (TLR3, TLR4) which play an important role in antimicrobial immune responses. In addition, PRAME expression in leukemic cell lines is rapidly induced by signalling pathways, which are activated in response to infection and inflammation.

PRAME Gene Editing Services

CRISPR/Cas9 Platform^CB at Creative Biogene 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 PRAME genes knockout/knockin/point mutation in cells or animals via CRISPR/Cas9 technology.

Service	Details	Alternative cell lines or animal species
PRAME Gene Editing Cell Line Generation	gRNA design and synthesis Transfect the cell lines you're interested Select the high expression cells and sort monoclonal cell Validate the knockout/knockin/point mutation of PRAME by PCR and sequencing Provide cryogenically preserved vials of stable cells and final reports	HEK239T, Hela, HepG2, U87, Ba/F3, CHO, MDA-MB-453, MDA-MB-231NIH3T3, T47D, Neuro2a, MCF7, RKO, K562, RAW264.7, etc.
PRAME Gene Editing Animal Model Generation	PRAME gene conventional knockout animals PRAME gene conditional knockout animals PRAME point mutation animals PRAME knockin animals	Mouse, rat, rabbit, zebrafish, C. elegans, etc.

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