As one of the deadliest types of cancer, pancreatic cancer (PC) possesses dense desmoplastic stroma and hypervascularity. Due to its complex biology (such as the high heterogeneity, inefficient drug penetration, and desmoplastic tumor microenvironment), conventional chemotherapy, radiotherapy, and targeted therapies have little benefit on the survival of patients with advanced PC. Nucleic acid therapy can modify pathogenic and drug-resistant genes, insert tumor suppressor genes, and has great potential in PC therapy. Alfa Oncology understands nucleic acid and pharmaceutical services and is committed to integrating our nucleic acid production and nucleic acid drug delivery system development capabilities to help our customers achieve nucleic acid therapy development.
Overview of nucleic acid drugs
In recent years, nucleic acids have emerged as extremely promising drug candidates for the treatment of a wide range of diseases, including pancreatic cancer (PC). In addition to small molecules and antibodies, nucleic acid drugs have been considered the third major drug discovery platform. Depending on the chemical structure and mechanism of action, nucleic acid drugs include antisense oligonucleotides (ASOs), small interfering RNAs (siRNA), circular RNA (circRNA), microRNAs (miRNAs), aptamers, decoys, and CpG oligodeoxynucleotides. The main advantage of nucleic acid-based drugs is that their pharmacokinetics are based on chemical entities and their base sequences determine their targets, allowing them to exhibit safety properties and effective pharmacodynamics.
|These nucleic acid drugs provided at Alfa Oncology|
|Antisense oligonucleotides (ASO)||Single-strand DNA/RNA||-mRNA
|-Cleavage mRNA (RNase-H)
|Small interfering RNA(siRNA)||Double-strand RNA
(hair-pine type is single-strand)
|mRNA||Cleavage mRNA (RNA interference)|
|Circular RNA (circRNA)||Covalently closed single-stranded RNA
(without free 5' and 3' ends)
|MicroRNA (miR, miRNA)||Double-strand RNA (Pre-miRNA is single-strand)||mRNA||miRNA replacement (RNA interference)|
|Aptamer||Single-strand DNA/RNA||Protein (Outside of cells)||Inhibits the physiological effect|
Antisense oligonucleotide (ASO) drug is one of many nucleic acid drugs and the first FDA-approved nucleic acid drug. We offer ASO drug development services for PC, mainly including ASO molecular size and sequence design, ASO manufacturing, and ASO chemical modifications.
Similar to antisense oligonucleotide (ASO) drugs, siRNA drugs require modifications to inhibit nuclease degradation and avoid induction of innate immune responses. However, unlike highly modified ASO drugs, siRNA drugs usually require a suitable delivery system due to their larger size and negative charges. 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.
The introduction of tumor suppressor miRNAs as well as oncogenic miRNA antagonists may have anti-cancer effects, inhibit pancreatic cancer cell proliferation and invasion, and promote apoptosis, providing a basis for the application of miRNAs in PC therapy. Our in-depth understanding of the molecular mechanisms behind the role of miRNAs in PC behavior can help in the design and production of natural and chemically modified RNAs and the development of new PC-targeted therapies.
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. We support the development of circRNAs therapeutics, providing circRNA design and optimization, circRNA chemical manufacturing and control (CMC), and circRNA-based drug delivery system development services.
Aptamers are characterized by targeted selectivity, simple modification, high potential affinity, scalability, and low immunogenicity, thus they have become a novel targeted theranostic platform as well as a drug delivery system for PC. In addition to helping customers to develop direct-acting cancer aptamers, we also provide aptamer-drug conjugates (AptDC) development service for PC, involving RNA AptDC, DNA AptDC, and aptamer-siRNA conjugates.
The major limitation of nucleic acid drugs is their delivery to the target tissue and cells, as well as in tuning their expression in cancer cells. With advances in the production and modification of nucleic acid therapeutic delivery systems, the application of nucleic acid drugs for PC treatment has been greatly facilitated. We are dedicated to offering a series of optimal PC nucleic acid therapeutic delivery vehicles, including viral vectors, LNPs, and exosomes.
We are committed to helping our customers to develop reliable, highly potential nucleic acid 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. If you are interested in our services, please contact us for more details.