Chronic lymphocytic leukemia (CLL) is a neoplasm originating from mature B lymphocytes. The clinical heterogeneity of CLL is extremely large. Some patients do not need treatment for life, while some patients survive for less than 3 years despite active clinical intervention. Therefore, it is necessary to further explore the molecular mechanism of CLL in order to find effective drugs for the treatment of CLL as soon as possible. CD Biosciences provides precise in vivo transfection services for lymphocytes to assist in the study of the molecular functions of chronic lymphocytic leukemia-related genes.

Target Genes Delivered in vivo in Chronic Lymphocytic Leukemia

Figure 1.

So far, multiple recurrent gene mutations involved in the occurrence and development of CLL have been discovered through whole exome sequencing (WES) and whole genome sequencing (WGS), and it has been confirmed that CLL has strong heterogeneity at the molecular level. Related reports have found that among these related mutated genes, NOTCH1 has the highest mutation frequency, and mutations in the non-coding regions of NOTCH1 and PAX5 have also been found. Another study showed that CLL also harbors mutations in non-coding and regulatory regions of ATM, TCL1A, IKZF3, SAMHD1, and BIRC3. The mutated genes found in this study are involved in multiple signaling pathways and physiological processes, including NOTCH signaling pathway, B cell receptor (BCR) signaling pathway, DNA damage repair and cell cycle regulation, apoptosis, epigenetic regulation and RNA Cutting and transporting etc.. Among them, the frameshift mutation of the NOTCH1 gene coding region and the mutation of the NOTCH1 3'-UTR region both lead to high expression of NOTCH1 protein, thereby promoting the activation of the NOTCH1 pathway; the functional inactivation mutation of FBXW7 makes it unable to effectively degrade NOTCH1 protein and promotes high expression of NOTCH1 protein; In addition, SF3B1 mutations promote NOTCH1 signaling pathway activation by altering DVL2 transcript splicing. Mutations of BIRC3, MYD88, TRAF3 and SAMHD1 genes involved in inflammation-related pathways, ITPKB, CARD11, EGR2 and IRF4 gene mutations in BCR pathway and B cell transcriptional regulation, and NRAS, KRAS, BRAF and MAP2K1 gene mutations in MAPK-ERK pathway all can participate in the occurrence and development of CLL by activating the NF-кB signaling pathway. TP53 and ATM deletion and (or) mutation leads to abnormalities in DNA damage repair and apoptosis pathways. Mutations in genes such as CHD2, ASXL1, HIST1H1B, HIST1H1E, ZMYM3, IKZF3, and BAZ2A lead to epigenetic abnormalities in CLL. Mutations of SF3B1 (RNA splicing factor) lead to widespread abnormalities in RNA splicing, resulting in abnormalities in multiple biological processes including DNA damage repair, telomere stability, and NOTCH signaling pathways; in addition, other mutated genes involved in RNA splicing process include MED12, ZNF292, NXF1, XPO1, DDX3X, XPO1 and RPS15, etc..

In addition to the above genes, there are interesting chronic lymphocytic leukemia-related genes that need to be explored and studied. Therefore, there is a need for an in vivo transfection system that can precisely target Chronic lymphocytic leukemia 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 chronic lymphocytic leukemia tissues and cells, and is toxic to the body;
• The in vivo transfection system used cannot penetrate the chronic lymphocytic leukemia 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 chronic lymphocytic leukemia 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. Nabhan C, Rosen ST. Chronic lymphocytic leukemia: a clinical review. JAMA. 2014, 312(21): 2265-2276.
2. Puente XS, et al.; Non-coding recurrent mutations in chronic lymphocytic leukaemia. Nature. 2015, 526(7574): 519-524.
3. Landau DA, et al.; Mutations driving CLL and their evolution in progression and relapse. Nature. 2015, 526(7574): 525-530.
4. Burns A, et al.; Whole-genome sequencing of chronic lymphocytic leukaemia reveals distinct differences in the mutational landscape between IgHVmut and IgHVunmut subgroups. Leukemia, 2017.
5. Wang L, et al.; Transcriptomic characterization of SF3B1 mutation reveals its pleiotropic effects in chronic lymphocytic leukemia. Cancer Cell. 2016, 30(5): 750-763.
6. Damm F, et al.; Acquired initiating mutations in early hematopoietic cells of CLL patients. Cancer Discov. 2014, 4(9): 1088-1101.

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