MicroRNAs (miRs, miRNAs) play an important role in tumorigenesis, cell proliferation, differentiation, invasion, angiogenesis, and metastasis by activating or inhibiting oncogenic molecular pathways across multiple cancer types. As one of the deadliest types of cancer, pancreatic cancer (PC) has a survival rate of only about 2% within 5 years of diagnosis. miRNA-based therapy is a powerful tool for cancer prevention and therapy with two main strategies, namely inhibition of oncogenic miRNA (oncomiRs) or increasing the level of tumor suppressor miRNAs. Alfa Oncology' in-depth understanding of the molecular mechanisms behind the role of miRNAs in PC behavior can help our clients identify new molecular targets and develop new PC-targeted therapies.
miRNA in PC
miRNAs may function as tumor suppressors or oncomiRs, and their expression is frequently dysregulated in tumors. Tumor suppressor miRNAs typically suppress the expression of oncogenes and genes that promote cell proliferation, migration/invasion and tumorigenesis. While oncomiRs promote cancer development by negatively regulating tumor suppressor genes. Previous studies have shown that the expression of oncomiRs is increased in cancer cell lines and patient tumors, while the expression of tumor suppressors tends to be reduced, stopped/ or lost. Thus, miRNAs are potential targets for therapeutic interventions. miRNA-based drugs, including inhibition of oncomiRs or activating of tumor suppressor miRs, have great potential as molecular therapeutic targets.
Based on miRNA analysis of in vitro models and pancreatic ductal adenocarcinomas (PDAC) patient samples, a large number of miRNAs are found to be dysregulated in PC. The miRNAs significantly overexpressed in PDAC include miR-10b, miR-21, miR-23a, miR-31, miR-100miR-143, miR-145, miR-146a, miR-150, miR-155, miR-181a/b/c, miR-196a/b, miR-21, miR-210, miR-221, miR-222, miR-223, miR-376a and miR-301. The miRNAs with down-regulated expression in PDAC include miR-148a, miR-217, miR-34a and miR-375. In addition, about 439 differentially expressed miRNAs are identified in PDAC samples, indicating that some of them are useful PDAC biomarkers.
The service offering at Alfa Oncology
The introduction of tumor suppressor miRNAs as well as oncogenic miRNA antagonists may have anti-cancer effects, inhibit PC cell proliferation and invasion, and promote apoptosis, providing a basis for the application of miRNAs in PC therapy. We have the capability to design and produce natural and chemically modified RNA.
- miRNA design and synthesis
We focus on miRNA mimics and inhibitors. During miRNA mimics design and production, we use multiple chemical modifications to improve their stability, binding affinity, protection against nucleases, and pharmacokinetic properties. While miRNA inhibitors are designed to specifically block the upregulated expression of miRNAs associated with cancer development. We can target specific miRNAs and produce related antisense oligonucleotides (ASOs) or antagomir.
- miRNA modifications
Since RNA molecules are quite unstable due to their 2'-OH chemical group. We offer a series of chemically modifications to stabilize and reduce the high reactivity of RNA molecules, including 2'-O-methyl (2'-OMe), locked nucleic acid (LNA), and phosphorothioate.
- Development of miRNA delivery system for PC therapy
In addition to stability, another challenge for miRNA-based therapies is the delivery of these RNA drugs to the desired site of action. There is an urgent need to select and design effective vectors for miRNA delivery through the dense fibrous stroma of PC. Through our advanced delivery system platform, we can provide viral vectors, lipid nanoparticles (LNPs) and exosomes to further facilitate the development of miRNA-based drugs for PC.
For more details on how we advance your innovation miRNA drug development projects, please feel free to contact us. We are ready to assist you.
- Chu, Xiangyu, et al. "MicroRNAs as potential therapeutic targets for pancreatic cancer." Chinese Medical Journal 135.01 (2022): 4-10.
- Gurbuz, Nilgun, and Bulent Ozpolat. "MicroRNA-based targeted therapeutics in pancreatic cancer." Anticancer research 39.2 (2019): 529-532.
- Fesler, Andrew, and Jingfang Ju. "Development of microRNA-based therapy for pancreatic cancer." Journal of pancreatology 2.04 (2019): 147-151.