Multiple myeloma (MM) is a clonal proliferative disease of bone marrow plasma cells, which mainly occurs in middle-aged and elderly people. The incidence of MM has obvious geographical and ethnic differences. The incidence of MM accounts for 10% of the total number of hematological tumors, and it is the second most common hematological malignancy after malignant lymphoma. Monoclonal immunoglobulin or its fragments (also known as M protein) appear in the blood and urine of patients with myeloma, causing damage to the function of related target organs such as bone marrow hematopoiesis, kidneys, and bones; the main clinical manifestations are anemia, bone pain and osteolytic destruction, renal insufficiency, repeated infections, etc. The complex genetic changes and chromosomal instability of MM cells, as well as the interaction between tumor cells and the bone marrow microenvironment, jointly promote the proliferation and survival of MM cells and resist drug killing. In-depth understanding of the biological characteristics of MM cells and tumors, clarifying the biological mechanisms related to the occurrence and development of MM, and then discovering new early warning, accurate diagnostic biomarkers, and potential drug targets can improve the clinical diagnosis and treatment strategies of MM.

Target Genes Delivered In Vivo in Multiple Myeloma

Figure 1. A cellular wiring diagram of a typical myeloma cell.(Morgan GJ, et al.; 2012)

Due to the instability of the genome, the occurrence of MM is accompanied by many expression of abnormal gene, gene structure variation, dysregulation of signaling pathways and epigenetic changes in the genome. The researchers systematically studied the gene expression profile of tumor cells in MM patients by gene chip detection technology. The results showed that the newly diagnosed MM patients could be divided into 7 subgroups (PR, LB, MS, HY, CD-1, CD-2, MF), 7 subgroups of patients showed significant differences in biological characteristics such as tumor cell proliferation activity, drug sensitivity, and patient survival time.     Chromosomal instability (CIN) is common in MM cells, and a variety of chromosomal instability genes are highly expressed, such as NEK2, TOP2A, AURKA, CCNB1, etc.. Further research found that the high expression of these CIN genes involved in the occurrence and development of MM disease. The expression of CIN gene NEK2 in tumor cells of MM patients is significantly increased, and the expression of NEK2 is further increased in tumor cells when the disease recurs. NEK2 promotes the proliferation of MM cells by activating downstream Akt, NF-κB, Wnt and other signaling pathways MM cells survive, and mediate the resistance of MM cells to a variety of drugs by up-regulating the expression of ABCB1, ABCG2, ABCC1 and other genes. In addition, it has been reported that high expression of NEK2 can also promote the resistance of MM cells to proteasome inhibitors by stabilizing the expression of the autophagy-related protein Beclin-1. Another study found that MM cells regulate the expression level of bone disease-related factor HSPE through high expression of NEK2. MM cells produce and secrete HSPE in large quantities. HSPE binds to the surface receptors of osteoclast precursor cells located in the bone marrow microenvironment to induce the maturation and differentiation of osteoclasts, thereby promoting the occurrence and development of myeloma bone disease.

In addition to the above genes, there are interesting multiple myeloma-related genes that need to be explored and studied. Therefore, there is a need for an in vivo transfection system that can precisely target multiple myeloma 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 multiple myeloma tissues and cells, and is toxic to the body;
• The in vivo transfection system used cannot penetrate the multiple myeloma 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 multiple myeloma 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. KUMAR S K, et al.; Multiple myeloma. Nat Rev Dis Primers. 2017, 3: 17046.
2. ZHAN F, et al.; The molecular classification of multiple myeloma. Blood. 2006, 108(6): 2020-8.
3. ZHOU W, et al.; NEK2 induces drug resistance mainly through activation of efflux drug pumps and is associated with poor prognosis in myeloma and other cancers. Cancer Cell. 2013, 23(1): 48-62.
4. XIA J, et al.; NEK2 induces autophagy-mediated bortezomib resistance by stabilizing Beclin-1 in multiple myeloma. Mol Oncol. 2020, 14(4): 763-78.
5. FRANQUI-MACHIN R, et al.; Destabilizing NEK2 overcomes resistance to proteasome inhibition in multiple myeloma. J Clin Invest. 2018, 128(7): 2877-93.
6. TERPOS E, et al.; Myeloma bone disease: from biology findings to treatment approaches. Blood. 2019, 133(14): 1534-9.
7. Morgan GJ, et al.; The genetic architecture of multiple myeloma. Nat Rev Cancer. 2012, 12(5):335-48.

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