Glioblastoma (GBM) is the most common primary malignant tumor, accounting for 47.1% of primary central nervous system tumors. The prognosis is extremely poor, with a 5-year survival rate of less than 5%. GBM cells are highly invasive and diffuse, making complete surgical resection difficult. In addition, GBM is highly resistant to radiotherapy and chemotherapy, so precise gene-targeted therapy is an important direction for future treatment. It is of great clinical significance to find gene targets related to the pathogenesis and malignant progression of GBM.

Target Genes Delivered in vivo in Glioblastoma

Through bioinformatics analysis, 76 differentially expressed genes were found in GBM. The enrichment analysis of differentially expressed genes found that these genes were significantly enriched in the positive regulation of angiogenesis, antigen presentation and processing, signal transduction, and regulation of autophagy. This suggests angiogenesis is a important role in GBM, with glioblasts promoting angiogenesis through a variety of pathways, including vascular sprouting growth, vascular intussusception, microcirculatory conduits formed by tumor cells through self-deformation and matrix deformation, and recruitment and differentiation of endothelial cells. These meet the needs of tumor cells for blood. In addition, the reduction of antigen presentation also plays an important role in the occurrence and development of GBM. The antigen-presenting cells of GBM include microglia and dendritic cells. The GBM microenvironment causes the antigen-presenting cells to decrease their ability to present antigens through various mechanisms, thereby suppressing the antitumor immune response.

Figure 1. Intracranial delivery of synthetic mRNA to suppress glioblastoma: Molecular Therapy. (Peng H, et al.; 2021)

POSTN

POSTN is an important cell matrix protein. POSTN regulates the composition of the extracellular matrix and the interaction between cells and the matrix by binding to a variety of extracellular matrix proteins such as fibronectin, type I collagen, and tenascin C, thereby regulating the adhesion and migration ability of tumor cells, which greatly promotes their invasion and metastasis in the tumor microenvironment. Multiple studies have found that POSTN is closely associated with the highly aggressive and metastatic features of gliomas. In recent years, studies have further confirmed that the expression of POSTN is closely related to the disease grading, progression and prognosis of glioma. The patients with high POSTN expression have significantly shortened survival and poor prognosis, which can be used as an independent prognostic factor for glioma patients.

CALD1

CALD1 is an actomyosin-related cytoskeletal protein that resides in contractile filaments and plays an important role in the regulation of cellular contractility and adhesion-dependent signaling. Studies have found that the overexpression of CALD1 can act on the contractility of vascular constituent cells and enhance the permeability of microvessels, thereby promoting the extravasation and migration of cancer cells. The study found that in the process of glioma neovascularization, the expression level of CALD1 gene splice variant and protein were significantly up-regulated, and it could improve the migration and invasion ability of glioma cells.

EPCAM

EPCAM is a tumor-associated antigen that can regulate cell cycle progression and cell differentiation. Several studies have confirmed that EPCAM is an extremely valuable target in the prognosis and treatment of various cancers, but the relationship between EPCAM and glioma is less studied. In recent years, studies have gradually realized that the high expression of EPCAM is closely related to the malignancy of glioma, the proliferation of glioma cells, the density of glioma microvessels and the prognosis of patients, and is an independent prognostic factor for the overall survival of patients with glioma.

TAGLN

TAGLN is a member of the microfilament connexin family, an actin cross-linking protein that is extremely sensitive to cell transformation and morphological changes, and is involved in the changes of smooth muscle cytoskeleton structure and function. The promotion of epithelial-mesenchymal transition and the alteration of cytoskeleton by TAGLN are important mechanisms by which TAGLN promotes the formation, migration and invasion of tumor cells. Significant association of TAGLN with tumor cell differentiation, infiltration and metastasis has been demonstrated in various tumor types.

In addition to the above genes, there are interesting glioblastoma-related genes that need to be explored and studied. Therefore, there is a need for an in vivo transfection system that can precisely target glioblastoma 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 glioblastoma tissues and cells, and is toxic to the body;
• The in vivo transfection system used cannot penetrate the glioblastoma 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 glioblastoma 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. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature. 2011, 473(7347):298-307.
2. Wang H, et al.; Stromal protein periostin identified as a progression associated and prognostic biomarker in glioma via inducing an invasive and proliferative phenotype. Int J Oncol. 2013, 42(5):1716-24.
3. Zheng PP, et al.; Differential expression of splicing variants of the human caldesmon gene (CALD1) in glioma neovascularization versus normal brain microvasculature. Am J Pathol. 2004,164(6):2217-28.
4. Ni J, et al.; Epithelial cell adhesion molecule (EpCAM) is involved in prostate cancer chemotherapy /radiotherapy response in vivo. BMC Cancer. 2018,18(1) :1092.
5. Weng YQ, et al.; The level of transgelin related to the function of dendritic cells pulsed with liver cancer. Zhonghua Gan Zang Bing Za Zhi. 2008,16(7):514-8.
6. Peng H, et al.; Intracranial delivery of synthetic mRNA to suppress glioblastoma. Mol Ther Oncolytics. 2021, 24:160-170.

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