Gastrointestinal stromal tumors (GISTs) are the most common gastrointestinal stromal tumors. GIST is derived from smooth muscle rhythm cells such as interstitial cells of Karnofsky. GIST is also the most common gastrointestinal soft tissue sarcoma in adults, with a global incidence of approximately 1.1/100,000.

Target Genes Delivered in vivo in Gastrointestinal Stromal Tumor

• c-Kit Gene Mutation

In 1998, Hirota et al., first discovered c-kit gene mutation in GIST. The mutation causes tyrosine kinase to continue to activate spontaneously without ligand stem cell factor binding and activate downstream signal transduction, thus suggesting that c-kit gene mutation is the main factor of pathogenesis of GIST. In GIST, c-kit gene mutation accounts for 75%~80%, of which exon 11 mutation is the most common (65%~70%), followed by exon 9 mutation (10%), exons 13 and 17 Mutations are rare. Exon 11 encodes the intracellular juxtamembrane KIT protein, which achieves an auto-inhibitory conformation by preventing the activation of the kinase activation loop. The mutation of exon 11 destroys the auto-inhibitory mechanism and enables the spontaneous activation of the kinase. In GIST, mutation patterns include point mutation, deletion mutation and insertion mutation. Exon 11 mutations in GIST can occur anywhere in the gastrointestinal tract, most commonly in the stomach, and histologically specific for spindle cells, where deletion mutations have a poor prognosis. Exon 9 encodes an extracellular near-membrane ligand-binding domain. After mutation, the kinase is activated by simulating the conformational change after binding with the ligand. The main mutation of exon 9 is insertion mutation, which mostly occurs in small and large intestinal GIST. Exon 13 encodes the ATP-binding region of the kinase. The mutation mode is mainly point mutation, which mainly occurs in gastric GIST.  Histologically, it mainly shows spindle cells. Exon 17 encodes a kinase activation loop, and the mutation mode is mainly point mutation, which mostly occurs in small intestinal GIST.

• PDGFRA Gene Mutation

In 2003, Heintich et al., found PDGFRA gene mutation in GIST without c-Kit gene mutation, suggesting that PDGFRA gene mutation is also the pathogenesis of GIST. In GIST, PDGFRA gene mutations account for 5% to 10%, mainly in exon 18 mutations, and rarely in exons 12 and 14. PDGFRA gene mutation GIST most commonly occurs in the stomach, and histologically, it is often epithelial or mixed. Exon 18 encodes an intracellular tyrosine kinase domain that stabilizes the kinase activation loop. The D842V mutation in exon 18 accounts for about 70% of all PDGFRA gene mutations and occurs only in GIST of the stomach, omentum, and mesentery. Exon 12 is homologous to the c-Kit11 exon, and mutation can lead to the loss of kinase autoinhibition function.

Figure 1. Signaling pathways of molecular GIST subtypes. (Blay JY, et al.; 2021)

In addition to the above genes, there are interesting gastrointestinal stromal tumors-related genes that need to be explored and studied. Therefore, there is a need for an in vivo transfection system that can precisely target gastrointestinal stromal tumors 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 gastrointestinal stromal tumors tissues and cells, and is toxic to the body;
• The in vivo transfection system used cannot penetrate the gastrointestinal stromal tumors 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 gastrointestinal stromal tumors 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. Hirota S, et al.; Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science.1998, 279(5350): 577-580.
2. Heinrich MC, et al.; PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003, 299(5607): 708-710.
3. von Mehren M, Joensuu H. Gastrointestinal Stromal Tumors. J Clin Oncol. 2018, 36(2): 136-143.
4. Blay JY, et al.; Gastrointestinal stromal tumours. Nat Rev Dis Primers. 2021, 7(1):22.

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