In the March Issue
• New! Aptamers in Drug Development Webinar
• History of Aptamers and Antibodies
• Aptamers in Oncology: Early Detection and Targeted Drug Delivery
New! Aptamers in Drug Development Webinar
Base Pair recently 
presented at the LabRoots virtual drug discovery conference. The latest webinar includes a review of aptamer advantages and recent aptamer-based publications in target discovery, drug delivery, therapeutic aptamers, small molecule drug detection, imaging / drug distribution, biomarker analysis, and drug monitoring. View the Aptamers in Drug Development webinar.
History of Aptamers and Antibodies
Have you seen the latest article from Base Pair?
Aptamers and aptamer selection were first discovered in 1990, but only one therapeutic aptamer has been approved by the FDA. How does the timeline for therapeutic aptamer development compare to antibody-based therapeutics? What specific challenges have delayed the development of therapeutic aptamers and what unique opportunities currently exist?
Click here to view the article.
Aptamers in Oncology: Early Detection and Targeted Drug Delivery
Identification of novel biomarkers, early detection, and drug toxicity are ongoing challenges in oncology. For some cancers, symptoms are only evident after cancer has progressed. For others, treatment is associated with debilitating side effects or hindered by drug resistance.
For many forms of cancer, researchers are generating promising new data with aptamers. Read about the most recent aptamer-based developments in oncology below and visit our Aptamers in Drug Discovery & Development page to learn more.
Brain Cancer
Researchers at the City of Hope in California discovered an RNA aptamer selective for the ectodomain of human PDGFRα, present on glioblastoma cells. Using flow cytometry and confocal microscopy, Cy3-labeled aptamer was shown to be selectively internalized into glioblastoma cells. Aptamer binding to PDGFRα was shown to suppress the expression of STAT3, ultimately leading to p53 upregulation and apoptosis, suggesting potential as a therapeutic agent for the treatment of glioblastoma (6).
Breast Cancer
Researchers in Korea conjugated the 18F radioisotope to a HER-2 specific aptamer to evaluate the aptamer for in vivo molecular imaging. The aptamer showed strong binding to HER-2 positive breast cancer cells and minimal binding to HER-2 negative cells in flow cytometric analysis, confocal microscopic images, and in vivo PET molecular imaging. While the aptamer showed utility as a diagnostic/prognostic tool, it may also be utilized for therapeutic targeting of HER-2 positive breast cancer cells (3).
Gastric Cancer
Researchers in China utilized serum from gastric cancer patients for positive selection and serum from patients with other forms of cancer for negative selection to discover aptamers with selective recognition of gastric cancer serum. Aptamer binding was further characterized using mass spectrometry to identify four potential protein biomarkers. These aptamers could potentially be utilized for detection of gastric cancer (7).
Leukemia
A team in Slovakia recently demonstrated feasibility of a biosensor for detection of leukemia cells positive for protein tyrosine kinase 7 (PTK7) in serum using an acoustic TSM (thickness shear mode) sensor. The sensor records changes in resonant frequency and motional resistance. A decrease in resonant frequency indicates binding of cells at the sensor surface. The biosensor achieved a lower limit of detection of 195 +/- 20 leukemia cells/mL in serum diluted 1:20. Biosensors for detection of specific cell types are showing exciting promise in diagnostics (4).
Liver Cancer
A multi-national research team used a selective aptamer to improve the specificity of the drug cabaxitaxel for MEAR hepatocellular carcinoma (HCC) cells. Confocal laser scanning microscopy (CLSM) and flow cytometry confirmed selective uptake of the aptamer-liposome-drug complex by MEAR cells. Aptamer-liposome-drug complexes stained with DiI, a lipophilic stain, demonstrated increased accumulation at the tumor site over time. Use of the complex gradually decreased tumor size without causing the decline in body weight associated with cytotoxicity. Aptamer-modified liposomal cabazitaxel decreased toxicity while improving drug effectiveness (2).
Lung Cancer
Researchers in Naples, Italy utilized an aptamer-miRNA conjugate to achieve targeted delivery to non-small cell lung cancer (NSCLC) cells expressing the AXL transmembrane receptor. They confirmed that the miRNA was delivered into AXL-expressing cells and reduced proliferation. They further confirmed that aptamer-miRNA-mediated reduction of AXL-expressing NSCLC cells decreased resistance to the drug erlotinib, an epidermal growth factor inhibitor (5).
Prostate Cancer
A research team in China utilized in vivo SELEX in a mouse model to discover bone-targeting aptamers selective for bone metastasis in prostate cancer. The selected aptamer showed higher levels of accumulation in bone than a control aptamer and higher accumulation in bone in tumor-bearing mice than control mice. Cy5-labeled aptamer bound to gold nanoparticles continued to accumulate in bone marrow endothelial cells, demonstrating potential for bone targeting in drug delivery (1).
Custom Aptamer Discovery
Base Pair has experience discovering aptamers to a wide range of targets, including proteins, peptides, small molecule drugs, metabolites, toxins, and live cells. With Base Pair’s patented multiplex SELEX, aptamers to multiple targets can be discovered in a single SELEX protocol.
Contact Base Pair today to learn more about aptamer selection.
References:
- Chen, L., et al. In vivo SELEX of bone targeting aptamer in prostate cancer bone metastasis model. International Journal of Nanomedicine. 2019. 14:149-159.
- Cheng, Y., et al. Cabazitaxel liposomes with aptamer modification enhance tumor-targeting efficacy in nude mice. 2019. 19:490-498.
- Kim, H.J., et al. PET imaging of HER2 expression with an 18F-fluoride labeled aptamer. 2019. Doi.org/10.1371/journal.pone.0211047.
- Poturnayová A. et al., DNA aptamers in the detection of leukemia cells by the thickness shear mode acoustics method. Chemphyschem. 2019. 20:1-11.
- Russo, V., et al. Aptamer-miR-34c conjugate affects cell proliferation of non-small-cell lung cancer cells. Molecular Therapy Nucleic Acids. 2018. 13:334-346.
- Yoon, S., et al. An RNA aptamer targeting the receptor tyrosine kinase PDGFRα induces, anti-tumor effects through STAT3 and p53 in glioblastoma. Molecular Therapy : Nucleic Acids. 2019. 14 :131-141.
- Zhang, Y., et al. DNA aptamers from whole-serum SELEX as new diagnostic agents against gastric cancer. RSC Advances. 2019, 9:950-957.