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Aptamer-Based Therapy Development for Pancreatic Cancer
Aptamers, also called chemical antibodies, are small oligonucleotide sequences that bind to their targets (such as proteins, bacteria, viruses, or cells) with high specificity and affinity. Due to its high tissue penetration, rapid production, low synthetic cost, low immunogenicity, thermal stability, and ease of labeling, aptamers have the potential to overcome difficulties of treatment in pancreatic cancer (PC), one of the deadliest diseases with high mortality and short overall survival time.
Overview of Aptamers
Aptamers refer to single-stranded oligonucleotides (DNA or RNA) of 20-100 nucleotides in length. They have a high affinity to the target markers, which is largely dependent on their unique three-dimensional structure, including loop, bugle, pseudoknot, G-quadruplex, and kissing hairpin.
Fig. 1 Application and development of aptamer in cancer: from clinical diagnosis to cancer therapy. (Han, Jing, et al.,2020)
Due to similar recognition mechanisms, aptamers are often compared to antibodies. Aptamers are generated and selected from an initially larger pool of oligonucleotides by a repetitive in vitro process, namely exponential enrichment of phylogenetic ligands (SELEX). The SELEX process involves the iterative enrichment of a pool of oligonucleotides. The pool and the targets are incubated together to allow the identification of some sequences of the target. Bounded sequences are then separated from unbounded sequences and finally amplification of bounded sequences is performed.
Comparison between Antibody and Aptamer
| Characteristic | Antibody | Aptamer |
|---|---|---|
| Targets | Mostly immunogenic macromolecular targets | Widely |
| Affinity | High | High |
| Cost | High | Medium |
| Synthetic method and time | cell culture (4-6 months) | chemical synthesis (2-3 months) |
| Immunogenicity | High | low |
| Tissue penetration | Slow | Fast |
| Modification | Conjugated with signaling or binding molecule | Versatile |
| Size | 50-100 kDa | 15-30 kDa |
| Stability | Susceptible to high temperatures | Fairly stable at ambient temperature |
| Toxicity | High | Low |
| Specificity | High | High |
Our Services
Aptamers are synthetic oligonucleotides that bind to specific target molecules with high affinity and specificity, acting as "chemical antibodies". They have emerged as a promising targeted therapy for cancer. Here are some strategies and techniques related to aptamer.
- Developing Aptamer-Based Drugs for Pancreatic Cancer
- Aptamer production
Aptamers are produced and selected by SELEX technology. Our improved SELEX technology is characterized by reduced sample injection, high separation efficiency, high degree of automation, and economy. We are dedicated to offering high-quality aptamers to satisfy our customers’ specific requirements.
- Aptamer modification
To improve aptamer's stability, specificity, pharmacokinetic, and pharmacodynamic properties, we are able to provide various biochemistry approaches to modify aptamers. Among them, chemical modification of aptamers is commonly used to increase the stability and applications of aptamers. Chimerization of aptamers is another type of modification that refers to binding to another aptamer, siRNA, protein, enzyme, biomolecule, or drug. Chimeric aptamers have greater stability and nuclease resistance and can be designed to bind specifically to tumor cells and deliver drugs to target cells.
- Developing Aptamer-Drug Conjugates of Pancreatic Cancer
In addition to helping customers to develop direct-acting cancer aptamers, we also provide aptamer-drug conjugates (AptDC) development service for pancreatic cancer, involving RNA AptDC, DNA AptDC, and aptamer-siRNA conjugates. Based on a range of pancreatic cancer preclinical models, we can perform a wide range of preclinical assessments, including but not limited to:
- AptDC formation and binding assay
- Targeting and internalization of AptDC specific to pancreatic cancer cells
- In vitro and in vivo cytotoxicity of AptDC
- Nuclease resistance assay
Why Choose Us?
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Aptamers offer an attractive targeted therapy for pancreatic cancer. Alfa Cytology is committed to advancing our clients' development of aptamer-based therapy for pancreatic cancer. For more about our services, please contact us. We are glad to work with you!
References
- Han, Jing, et al. "Application and development of aptamer in cancer: from clinical diagnosis to cancer therapy." Journal of Cancer 11.23 (2020): 6902.
- Xiang, Dongxi, et al. "Nucleic acid aptamer-guided cancer therapeutics and diagnostics: the next generation of cancer medicine." Theranostics 5.1 (2015): 23.
- Li, Q., et al. "Aptamers: a novel targeted theranostic platform for pancreatic ductal adenocarcinoma." Radiation Oncology 15.1 (2020): 1-12.
