In This Issue:
- Two new aptamer discovery & development scientists join Base Pair
- Generation of Cell-Specific Aptamers in Oncology
- Base Pair aptamer to Epirubicin small molecule chemotherapy agent
Truong Nguyen and Deepak Thirunavukarasu join Base Pair
Truong Nguyen received his bachelor of Engineering in Biotechnology from Nong Lam University in Vietnam. From 2006 to 2007, Truong worked for Pfizer Animal Health Vietnam (currently Zoetis Vietnam) as a technical consultant and project manager. He received a Master of Biotechnology from University of Queensland, Queensland, Australia where he focused on effects of neurotoxins on synaptic activity. In 2016, Truong received his Ph.D. in Biochemistry and Cell Biology from Rice University, Houston, Texas. His research focused on elucidating the dynamics of genetic network in the baker yeast Saccharomyces cerevisiae using a microfluidic device and fluorescence microscopy. Truong’s postdoctoral work at MD Anderson Cancer Center focused on the development of new biomarkers for early detection of liver cancer.
”I’m very excited to apply my multidisciplinary experience and technical expertise to support customer’s efforts in research and development at Base Pair.” -Truong
Deepak Thirunavukarasu is a molecular biologist with experience in aptamer selection.
Deepak completed his undergraduate studies at Anna University in Chennai, India. He received his Ph.D. in molecular biology from the State University of New York at Albany, where he developed conformation-specific RNA aptamers to Heat Shock Protein 70 for potential use in cancer therapy and neuro-degenerative diseases. Deepak’s post-doctoral work at the Scripps Research Institute focused on the generation of highly stable aptamers with 2’ sugar modifications. This work resulted in generation of the first 2’-fluoro-purine-modified DNA aptamers using an engineered DNA polymerase.
”I am excited about the potential of aptamer technology and I look forward to exploring new horizons for aptamer development with Base Pair Biotechnologies.” -Deepak
Generation of Cell-Specific Aptamers in Oncology
Aptamers are single stranded DNA or RNA oligonucleotides, ~30 – 80 bases in length, that form three-dimensional structures that can selectively bind to specific targets. Variations on the traditional SELEXTM aptamer selection process utilizing postoperative tissues and modified cells are being employed to develop highly selective aptamers for potential use in cancer diagnostics and therapeutics.
A team of researchers at the Krasnoyarsk State Medical University, Krasnoyarsk Research Center, and the Krasnoyarsk Regional Clinical Cancer Center in Russia and researchers at the University of Ottawa, Canada developed aptamers selective for lung cancer cells. Lung adenocarcinoma cells were isolated from post-operative tissue for positive selection. Healthy lung tissue from the same donors and whole blood from healthy donors were used for negative selection. Degree of enhanced binding to adenocarcinoma cells vs. controls was used to choose the final aptamer sequences. Using LC-MS analysis, potential protein targets were identified for each selected aptamer. Because individual aptamer sequences specific for lung cancer cells were shown to bind different cell surface markers, a pool of aptamer clones may offer enhanced detection. Taking a personalized medicine approach, the researchers suggest that tumor-specific aptamers could be produced for individual patients. The blood smear technique developed would facilitate tumor monitoring during treatment. Aptamers to specific cell types can be generated without prior knowledge of cell surface markers – particularly useful when working with a high degree of variability in surface marker expression. (2)
The researchers at Krasnoyarsk also utilized post-operative breast tissue to generate aptamers selective for breast cancer cells and tissue. This tissue-based SELEXTM utilized positive selection based on malignant tumor tissue from 11 patients. Negative selection utilized benign tumor tissue from 8 donors, lung cancer tissue samples, a glioblastoma tissue sample, and healthy breast tissue. DNA aptamers selective for breast cancer cells may be utilized to identify new diagnostic biomarkers and targets for therapy and to enable targeted delivery of anti-cancer drugs. (3)
Pancreatic cancer is often diagnosed at an advanced stage where there is little chance of effective treatment. Based on findings related to the role of cancer stem cells (CSCs) in the pathogenesis of cancer, researchers at the Yonsei University College of Medicine in Seoul, South Korea developed aptamers selective for circulating pancreatic tumor cells exhibiting the characteristics of cancer stem cells. In order to generate aptamers with this unique selectivity, researchers utilized the sphere-forming property of stem cells. Positive selection was performed with dissociated sphere cells generated from HPAC human pancreatic adenocarcinoma cells. Following aptamer selection, aptamer-binding cells showed a high level of CSC-related genes and expression of CSC-related cell surface markers, confirming specificity. Aptamer binding was actually shown to be co-localized with CD133, a rare surface marker in HPAC cells. Aptamers selective for stem cell-enriched circulating tumor cells may someday enable earlier diagnosis, via non-invasive screening, or be effective as direct therapeutic or drug targeting agents in the treatment of pancreatic cancer. (1)
Aptamers offer exciting opportunities in the field of oncology for diagnosis, biomarker / target discovery, therapeutics, and targeted drug delivery. The development of more sensitive, non-invasive screening methods is a first step in the application of aptamers as a new tool in the ongoing effort to treat a wide range of cancers.
Considering aptamers? Base Pair Biotechnologies can put together a customized development plan. Contact us today to learn more.
1. Kim, Y.J., Lee, H. S., Jung, D. E., Kim, J. M., and Song, S. Y. (2016), The DNA aptamer binds
stemness‐enriched cancer cells in pancreatic cancer. J Mol. Recognit. doi: 10.1002/jmr.2591
2. Zamay, G.S. et al. (2015) Aptamers selected to postoperative lung adenocarcinoma detect circulating tumor cells in human blood. Molecular Therapy. 23(9):1486-96. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817883/pdf/mt2015108a.pdf
3. Zamay, G. S. et al. (2016) Selection of DNA aptamers for breast cancer. Biochemistry (Moscow)
Supplement Series B: Biomedical Chemistry. 10:2, 158-164.
Aptamer to epirubicin small molecule used in chemotherapy
Epirubicin is a small molecule chemotherapy drug (543 daltons) that interferes with the synthesis and function of DNA. It is the 4’ epimer of the anthracycline antibiotic doxorubicin. Epirubicin, alone or in conjunction with other chemotherapy agents, is used to treat a number of cancers including breast, ovarian, stomach, lung, bowel, myeloma, and some types of lymphoma and leukemia. (1, 2, 3)
For epirubicin, the major acute dose-limiting toxicity is myelosuppression, or damage to bone marrow / reduction of cell formation in the bone marrow, with a marked reduction in white blood cells, or leucopenia. Cardiotoxicity is the major chronic cumulative dose-limiting toxicity. There is a clear dose-response for anthracyclines, so it is beneficial to maximize dosage while avoiding toxic levels to maximize effectiveness. (1)
Following injection, epirubicin undergoes rapid and extensive tissue distribution, especially to tissues with high blood flow, such as heart, liver, kidneys, spleen, lung, pituitary, intestine, and bone marrow, with accumulation in red blood cells. Rapid distribution is followed by an intermediate phase and slower terminal elimination phase. Patients with hepatic dysfunction have displayed elevated levels in plasma due to reduced clearance. (1)
The use of aptamers to generate rapid, sensitive detection methods for small molecule drugs can assist with proper dosing and ADME studies during drug development and facilitate monitoring of drug levels / adjustment of dosing schedule and drug concentration during chemotherapy regimens to maximize dosage and avoid damaging drug levels. The use of aptamers for specific cell targeting could potentially limit effects on normal cells for epirubicin and other small molecule drugs, reducing toxicity and common side effects.
Base Pair Biotechnologies has developed selective aptamers to several small molecules, including epirubicin, Base Pair product #ATW0006. We utilize proprietary methods to solubilize and present small molecules for aptamer selection and to accurately measure the affinity of aptamers for binding to small molecule targets. Contact Base Pair today to schedule a call with one of our experienced aptamer development specialists.
Contact Base Pair to learn more about recent aptamer projects and aptamer opportunities.
Visit www.basepairbio.com to view a complete listing of catalog aptamers available from Base Pair.
1. Plosker, Greg L. and Diana Faulds. (1993) Epirubicin. Drugs. 45(5):788-856.
drugs/epirubicin#general. Accessed March 6, 2017
3. https://pubchem.ncbi.nlm.nih.gov/compound/Epirubicin. Accessed March 6, 2017