Best Wishes for Safe & Happy Holidays and a Successful New Year from Base Pair!
In The December Issue:
- Openings at Base Pair
- New Plate-Based Assay Survey: Vote Today
- Aptamers in Theranostics: Targeted Drug Delivery
Base Pair Openings in Operations and Business Development
Base Pair has a new opening for a Senior Operations Associate at our headquarters in Pearland, Texas. The Senior Operations Associate will be responsible for procurement, order fulfillment, scheduling of equipment maintenance, and inventory management.
Base Pair is also interviewing candidates for a Senior Manager or Director of Business Development position. The Senior Manager or Director of Business Development will ideally be based in California and will report directly to the CEO. Visit the careers page to learn more.
Plate-Based Assay Survey
Base Pair is currently developing plate-based assays using oligonucleotide aptamers in place of antibodies.
Vote Now and tell us which analytes and assay features are most important to you.
Aptamers in Theranostics: Targeted Drug Delivery
In a recent study in Xi’an China, researchers developed an aptamer selective for CD123, a cell surface marker expressed on cancer cells in acute myeloid leukemia. They used this aptamer to demonstrate the ability of selective aptamers to deliver treatment directly to infected cells, enhancing anti-cancer drug activity and reducing off-target effects on normal cells. (4)
What is Theranostics?
As the name suggests, theranostics involves a blending of diagnostics and therapeutics, the use of diagnostic results to determine and apply patient-specific therapeutics. (2) In one sense, it is the new buzz word for personalized medicine, but it is gradually becoming much more. Some of the affinity reagents that have been utilized to detect biomarkers in vitro and deliver targeted treatment to specific patients are now being used to detect biomarkers in vivo and deliver targeted treatment to specific cells. The ability to selectively attack infected cells with minimal effect on normal cells is a huge advance in therapeutic treatment.
Cell Targeting with Aptamers
In part, the ability to target cells in vivo involves a class of affinity reagents called aptamers. Aptamers are short, single-strands of DNA or RNA (~30 to 100 nucleotides) that form unique secondary and tertiary structures which can selectively bind a specific target. A starting library of trillions of DNA or RNA sequences goes through several rounds of a process called SELEX to generate a smaller pool of target-selective aptamers. Next generation sequencing, bioinformatics analysis, and high throughput screening are used to narrow the pool to a handful of selective aptamer sequences. Aptamers can be highly selective for cells expressing a specific cell surface marker. Due to their small size and composition, they tend to be non-immunogenic and easily penetrate tissues, and sometimes cells. They are easily conjugated to fluorescent dyes or complexed with other molecules without compromising binding affinity. (1,3) These small, selective, easily-conjugated, non-immunogenic aptamers are ideal for in vivo cell targeting.
Aptamer Screening in Flow Cytometry
A major requirement of targeted drug delivery is cell selectivity. The best therapies will be highly selective for infected cells and have minimal effect on normal cell function. Flow cytometry is increasingly being applied to analyze aptamer selectivity for specific cell types and cell surface markers. In the CD123 study, fluorescein-labeled aptamer was incubated with CD123 peptide-, BSA-, IgG-, and trypsin-coated beads. The two selected CD123 aptamers demonstrated strong binding to the CD123 peptide and negligible binding to the common immune proteins tested. (4) While flow cytometry is a useful tool for aptamer screening, qualified aptamers can also be powerful diagnostic tools in flow cytometry and fluorescence-based imaging applications. (1)
Aptamer-Directed Drug Delivery
In order to deliver a therapeutic agent, it must somehow be complexed with the cell-selective aptamer. In the CD123 study, reseachers utilized an annealing ligand and two G/C-rich extender probes to build a targeted drug train, or TDT. First the aptamer (A) was bound to an annealing ligand (B). Probe 1 (C) and probe 2 (D) were then added, with Probe 1 annealing to both the ligand and Probe 2. Finally, the aptamer-probe complex was incubated with Doxorubicin (E), or Dox, a chemotherapy agent. The Dox intercalated with the DNA probes in the targeted drug train. (4)
Efficacy of Aptamer-Directed Therapeutics
The therapeutic effectiveness of the TDT was investigated both in vitro and in vivo. In order to evaluate in vivo efficacy, researchers injected tumor-bearing mice with free Dox, TDT, or saline. The TDT and free Dox groups saw a significant reduction in tumor size. The TDT group displayed the smallest tumors and longest survival, demonstrating enhanced therapeutic effects with targeted drug delivery. To investigate off-target effects in vivo, researchers assessed biomarkers in serum and major organs of treated, euthanized mice. Levels of inflammatory cytokines were increased in normal tissues from mice treated with Dox. Levels in the TDT group were comparable to the saline control group, demonstrating a reduction in effects on normal cells with targeted drug delivery. (4) This is one of many recent studies that have confirmed the utility of aptamers for targeted drug delivery. (1) Further studies, including pharmacokinetics and toxicity testing and clinical trials comparing aptamer-assisted methods to traditonal drug delivery, will be required to transition from the lab to the clinic.
Custom Aptamer Discovery
A key component in targeted drug delivery is the development of selective aptamers. Base Pair has selected aptamers to a wide range of targets, including secreted proteins, cell surface markers, metabolites, small molecule drugs, and viral proteins. Tell us a bit about your project so that we can propose an aptamer selection strategy for you. Request Information
References:
Image of stained melanoma cells courtesy of Julio C. Valencia, NCI Center for Cancer Research
- Chandola, C. et al. Application of aptamers in diagnostics, drug-delivery and imaging. Journal of Biosciences. 2016. 41(3):535-561. Application of aptamers in diagnostics, drug-delivery and imaging
- Collins Dictionary. https://www.collinsdictionary.com/us/submission/11018/Theranostics. Accessed December 6, 2017.
- Jayasena, S.D., et al. An emerging class of molecules that rival antibodies in diagnostics. Clinical Chemistry. 1999, 45(9):1628-50.
- Wu, H., et al. Novel CD123-aptamer-originated targeted drug trains for selectively delivering cytotoxic agent to tumor cells in acute myeloid leukemia theranostics. Drug Delivery. 2017. 24(1): 1216-1229