RNA interference (RNAi) is a process of sequence-specific post-transcriptional gene silencing triggered by short double-stranded RNAs, i.e., small interfering RNAs (siRNAs). Over the past two decades, in addition to serving as a powerful tool for gene function studies (such as loss-of-functional tests and target validation), RNAi technology has provided a potential treatment for human diseases, including pancreatic cancer (PC).
Overview of siRNAs and siRNA drugs
siRNAs are double-stranded RNAs (including the sense strand and the antisense strand) containing 19-21 nucleotides, which can be recognized by the RNAi machinery. Once a siRNA is taken up by a cell, it can be recognized by the RNA-induced silencing complex (RISC) and forms the siRNA-RISC complex in the cytoplasm. Then the sense strand can be cleaved by argonaute-2 (AGO2, a cleavage enzyme), and the antisense strand can form an activated AGO2-RISC complex with AGO2-RISC. The activated AGO2-RISC complex is able to search for and bind to an mRNA containing antisense active strand complementary sequences, followed by mRNA cleavage and inactivation. The silencing activity of siRNA is determined by a number of factors, such as the strand of double-stranded RNA that is ultimately used as the mRNA complementary strand and the ease of RISC formation. Since the approval of the first siRNA drug by the U.S. Food and Drug Administration (FDA) in 2018, clinical applications of siRNA drugs are rapidly expanding.
siRNA drug development for PC
Alfa Oncology fully supports your siRNA drug development project for PC. Our team of experts in bioinformatics, RNA biology, nucleic acid chemistry, and translational research work together seamlessly and efficiently. During siRNA drug development, our scientists have combined the rationale siRNA design, off-target effect prediction algorithms, the key features in nucleic acid chemistry, and related drug delivery system development. Our systematic functional platform has improved workflows and can accelerate turnaround time for various stages in siRNA drug development. We are committed to helping our customers to develop reliable, highly potential siRNA drugs with greater stability and less cellular toxicity. During the drug development process, we can provide our services in a modular and integrated manner according to the requirements of our customers. The specific services are as follows:
- siRNA design
- siRNA synthesis
- siRNA validation of target silencing
- siRNA drug delivery system development
- In vitro pharmacology and cell cytotoxicity assays
- In vivo pharmacology and safety assessment
Multiple targets to support ASO drug development for PC
- KARS point mutations
-Proto-oncogene tropomyosin receptor kinase A
- Survivin and nestin
-Bcl-2 family and transforming growth factor
Thanks for your interest in our siRNA drug development services for PC. For more details on how we advance your innovation siRNA drug discovery and development projects, please feel free to contact us. We look forward to working with you on your next project.
- Cuciniello, Rossana, Stefania Filosa, and Stefania Crispi. "Novel approaches in cancer treatment: preclinical and clinical development of small non-coding RNA therapeutics." Journal of Experimental & Clinical Cancer Research 40.1 (2021): 1-19.
- Won, Eun-Jeong, et al. "Gene Therapy Using Nanocarriers for Pancreatic Ductal Adenocarcinoma: Applications and Challenges in Cancer Therapeutics." Pharmaceutics 14.1 (2022): 137.