In addition to the lack of biomarkers for early diagnosis and prognostic assessment of pancreatic cancer (PC), targeted therapy for PC is also an unmet need due to the lack of molecular targets. Circular RNA (circRNA) is a group of endogenous non-coding RNAs (ncRNAs) possessing unique covalently closed circular loops. CircRNAs have been shown to be aberrantly expressed in different cancer tissues and cell types, including PC.
Circular RNA and PC
Although circRNAs can be derived from 3ʹ-UTR, 5ʹ-UTR, introns, or intergenic spacer regions, their main source is the exons encoding proteins. According to its origin, circRNA can be divided into three types, including intron-derived circular RNA, exon-derived circular RNA, and circular RNA composed of both exons and introns. Due to its unique closed-loop structure and lack of poly-A tails, circRNAs are more stable than linear RNA and tend not to be degraded by exonucleases. Moreover, circRNA is highly conserved in the evolution of species. There are several biological roles of circRNA, such as serving as a miRNA sponge, protein sponge, and translation template.
Fig. 1 Functions of circRNAs. (Rong, Zeyin, et al., 2021)
Numerous studies have highlighted that many circRNAs are deregulated in pancreatic ductal adenocarcinoma (PDAC) and play an important role in the development and progression of PC. They can act as oncogenes or tumor suppressors in PC, altering PC proliferation, migration, invasion, metastasis and apoptosis, and so on. There are multiple mechanisms and miRNA sponges remain the main mechanism associated with circRNAs in PC.
The service offering at Alfa Oncology
Since the circRNA performs complex, diverse functions by regulating miRNAs, lncRNAs, RNA-binding proteins, and transcription factors, targeting circRNAs can regulate not only multiple oncogenes but also miRNAs, so targeting circRNAs is a superior targeting strategy to targeting individual miRNAs or oncogenes. We support the following PC therapeutic strategies targeting circRNA, including antisense oligonucleotide, small interfering RNA (siRNA), and artificial circRNAs. Here, we focus on the development of circRNAs therapeutics, providing circRNA design and optimization, circRNA chemical manufacturing and control (CMC), and circRNA-based drug delivery system development services.
- CircRNA design and optimization
CircRNAs suffer from the inability to form a loop or from inefficient circularization. Our team of experts has put a lot of effort into the design and optimization of circRNA. At present, we are able to start with both circRNA overexpression vectors and circularization-mediating sequences to ensure accurate and efficient circularization of inserted circRNA.
- CircRNA CMC
With more mature processes and facilities for circRNA production, we can help our customers to achieve a certain scale of circRNA production. The CMC process for circRNA mainly includes plasmid construction and proof of concept, in vitro synthesis and purification, as well as circularization and purification.
- CircRNA-based drug delivery system development
Previous studies have revealed that nanoparticles could be a promising delivery system for circRNA-based drugs. Through our advanced delivery system platform, we can provide lipid-based nanoparticles (LNPs), gold nanoparticles (AuNPs), and exosomes to further facilitate the development of circRNA-based drugs for PC.
Fig. 2 The mechanism underlying circRNAs in the regulation of cellular properties and miRNA-related gene regulation networks in PC. (Rong, Zeyin, et al., 2021)
As related studies continue to progress, the role of circRNA in the occurrence and development of PC has been discovered and gradually recognized, suggesting that circRNAs are new biomarkers for PC early diagnosis and a focus of targeted therapy. With extensive knowledge of circRNA biogenesis, mechanism of action and its role in PC-targeted therapies and advanced nucleic acid drug development platforms, Alfa Oncology is committed to advancing our clients' development of circRNA-based therapy for PC. For more about our services, please contact us.
- Wang, Yi-Zhi, et al. "Research progress on circularRNAs in pancreatic cancer: emerging but promising." Cancer biology & therapy 20.9 (2019): 1163-1171.
- Rong, Zeyin, et al. "Circular RNA in pancreatic cancer: a novel avenue for the roles of diagnosis and treatment." Theranostics 11.6 (2021): 2755.
- Sun, Xinzhu, et al. "Recent Advances in the Potential Use of Circular RNA for the Diagnosis and Treatment of Pancreatic Cancer." Cancer Management and Research 13 (2021): 4251.