Cutaneous melanoma is probably the most dangerous skin tumor, and its lethality accounts for 90% of skin tumor deaths. The elderly is the most commonly affected population, and adolescents can also be affected. Melanoma not only occurs in the skin, but also involves the eyes and mucous membranes, manifesting as skin melanomas, genital and mucosal melanomas, and ocular melanomas.

Target Genes Delivered in Vivo in Melanoma

With the development of molecular biology, more and more melanoma-related genes have been discovered and studied. Studies have found that many genes are related to the occurrence, development, metastasis and prognosis of melanoma, such as BRAF, NRAS, KIT, GNAQ/GNA, NF1 and other genes. To advance the study of these related genes, we provide in vivo targeted transfection services for these genes.

Figure 1. Melanocyte differentiation: the MITF axis.( Flaherty KT, et al.; 2012)

BRAF

BRAF gene is located on human chromosome 7 and encodes a serine/threonine protein kinase that functions in the regulation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway, affects cell division, differentiation and secretion.  Studies have found that in clinical melanoma patients, the BRAF gene mutation rate is relatively high, and the main mutation site is V600E.  Currently, there are already marketed targeted drugs at this site approved by the FDA for the treatment of patients with advanced melanoma with BRAFV600 mutation.

NRAS

The murine sarcoma oncogene (ras viral oncogene homolog, RAS) is highly conserved in evolution, and the family has three members, namely H-ras, K-ras, and N-ras, and its encoded product is P2 protein. It has been reported in the literature that the mutation of the RAS gene in melanoma is mainly N-ras, and the common site is that the glutamine at codon 6 is replaced by leucine, which leads to the over-activation of the NRAS-encoded protein and the uncontrolled proliferation of cells. In 2017, the US FDA has recommended three groups of BRAF inhibitors and MEK inhibitors in combination for the treatment of patients with advanced melanoma with BRAFV600 mutation.

KIT

KIT gene, a member of the tyrosine kinase receptor family expressed on the cell surface, plays a role in the normal development of melanocytes, and its mutation and overexpression are responsible for the pathogenesis of acral lentigo and mucosal melanoma. Currently, drugs targeting KIT mutations are already in clinical trials. However, because the KIT mutation sites are not concentrated, the effect of tyrosine kinase inhibitors is poor. Therefore, the targeted therapy of KIT needs further exploration and research on the function of KIT.

GNAQ/GNA

GNAQ/GNA gene encodes the α subunit of the G protein (G protein)-coupled receptor, which has a low mutation rate in cutaneous melanoma and a high mutation rate in uveal melanoma and is a driver mutation gene. Therefore, it is one of the potential targets for the treatment of uveal melanoma.

NF1

TCGA reports that 4% of melanomas have mutations in the NF1 gene, of which about 50% are loss-of-function mutations. Existing studies have found that melanoma patients with NF1 gene mutations have a high mutation load, have obvious ultraviolet damage mutation characteristics, are more common in elderly men, and have poor prognosis. In addition, there have been reports that NF1 gene deletion is associated with tumor resistance to BRAF inhibitor therapy. Therefore, further research on the function of NF1 gene is one of the good ideas to find the treatment of melanoma.

In addition to the above genes, there are interesting melanoma-related genes that need to be explored and studied. Therefore, there is a need for an in vivo transfection system that can precisely target melanoma tissue and be taken up by tumor cells to function in vivo. The system can help researchers overcome various challenges encountered during in vivo transfection:

• Relevant molecular function studies can only be carried out in vitro, lacking important in vivo data
• Using in vitro transfection system for in vivo transfection, the transfection efficiency is very low;
• The in vivo transfection system used is not specific to melanoma tissues and cells, and is toxic to the body;
• The in vivo transfection system used cannot penetrate the melanoma tissue into the tumor tissue;
• The nucleic acid load of the in vivo transfection system is low, and it is difficult to achieve the expected effect;
• Etc…

Our Advantage:

• We can provide an in vivo transfection system for melanoma tissues and cells to achieve efficient transfection
• Our system can target multiple targets at the same time, improving targeting accuracy
• The in vivo transfection system has low toxicity to the body and is safe to use
• In vivo transfection system vectors can protect nucleic acids from degradation during in vivo delivery
• Persistent knockout effect in experimental animals after a single injection
• The system load is high, and the transfection needs of different doses can be completed
• Professional design and service team to provide you with reliable service and technical support
• Timely feedback of technical reports

CD BioSciences specializes in developing transfection systems and customizing transfection reagents for gene transfection using our core technologies. With our high-quality products and services, your transfection results can be greatly improved. If you can't find a perfect in vivo transfection system, you can contact us. We can provide one-to-one personal customization service.

References

1. Garbe C, et al.; European consensus-based interdisciplinary guideline for melanoma. Part: Diagnostics-Update 2029. Eur J Cancer. 2020, 26: 4-58.
2. Srivastava A, et al.; Molecular Diagnostics in Melanoma: An Update. Singapore: Springer. 2019, 73-88.
3. Cancer Genome Atlas Network. Genomic classification of cutaneous melanoma. Cell. 2015, 161(7):1681-96.
4. Gong HZ, et al.; The clinical significance of KIT mutations in melanoma: a meta-analysis. Melanoma Res. 2018, 28(4):259-270.
5. Flaherty KT, et al.; From genes to drugs: targeted strategies for melanoma. Nat Rev Cancer. 2012, 12(5):349-61.

* For research use only. Not for use in clinical diagnosis or treatment of humans or animals.