Aptamer, the new molecule in town: You can create your own and even name it!

Written by: Nur Nadia Razali & Dr. Chin Siok Fong

Date published: 6 April 2020


What is Aptamer? The exotic word originated from a Latin-Greek root. “Aptus” means to fit in Latin, while “meros” means part in Greek.  Aptamer is a short, chemically synthesized, single-stranded nucleic acid (DNA or RNA) that folds into unique three-dimensional conformation and binds to its target, specifically in a similar manner as antibody-antigen. The beauty of an aptamer lies in its versatility to bind to a plethora of molecules, i.e. the small molecules, ions, toxins, peptides, protein, viruses, bacteria and even the whole cells. Most importantly, aptamers demonstrate an unambiguous binding affinity which discriminates for the specific target with high precision and thus, undeniably high selectivity. This is the reason why aptamers are also known as “nucleic acid antibodies”.


Figure 1: Schematic diagram of the mechanism of aptamer and its binding target site


An amusing fact about aptamer is that it does not bind to the target by canonical base-pairing like oligonucleotides religiously do as commonly seen in a PCR reaction. This is because the ultimate target for an aptamer is NOT the DNA. This man-made molecule forms mainly through compatibility, electrostatic on van der Waals interactions, and hydrogen bond or combination of these effects. Essentially, it is created with unnatural base pair forming stems and loops that position bases in optimal locations fit for the binding structure as shown in Figure 1 (1). Therefore, the variability in aptamer sequences conveys them their flexibility (2).

It is important to highlight that aptamers are generated chemically. It can be engineered and modified to your desired design. In other words, it is produced entirely in-vitro, thus avoids the use of animals, contrary to conventional antibodies, in which the production of the latter has always been dampened by animal issues on top of the lengthy, delicate and resource-intensive process of the antibody development. These drawbacks not only resulting in high cost being passed onto the consumer but also uproars by the animal rights activists. With aptamers in town, this is absolutely a piece of good news for the animal lovers, who vowed to protect animals from any form of cruelty and harm.

Antibodies are no doubt the most widely used biomolecules for diagnostic assays on the market. Most of the diagnostic assays such as Enzyme-linked Immuno-Sorbent Assays (ELISAs), immunohistochemistry, immunofluorescence, western blotting, flow cytometry, immunoprecipitation and others, work by combining the high affinities of antibodies to their target antigen in a controlled lab environment. Unfortunately, conventional antibodies have limited shelf life, easily denatured and are inconsistent in quality and specificity due to batch variation. The production time may fluctuate up to months, subjected to contamination whereas aptamers can be easily synthesized in vitro and are stable at room temperature without the need for refrigeration. Furthermore, the antibodies raised in animals are considered a foreign matter if were to introduce into a human body as a therapy. The action may evoke an undesired immune response, especially when given in repeated doses causing serious complication to the patients. On the contrary, aptamers are nucleic acids that are not recognized by the body’s immune system as foreign, and thus do not evoke a negative immune response.


Figure 2: Advantages of aptamer and its benefits for clinical applications


Versatility of aptamers does not imply that one aptamer can bind to a variety of targets, but simply means each aptamer can be structurally designed to match the specific binding site of the target like a lock-and-key. For detection purpose, a reporter molecule that usually carries a fluorochrome can be conjugated to the aptamer at the desired position without compromising its molecular recognition function, thus enhanced its feasibility for various applications (3). Among the research areas where aptamers are increasingly in use are nanoparticle detection using microfluid device, dye profiling, drug therapy and as drug target validation. At a larger industrial scale, aptamers have been used in the diverse areas within biotechnology and therapeutic applications such as biosensors, diagnostics, anti-angiogenic agents and even in engaging infectious agents (4).

In summary, aptamers are tough chemical competitor to conventional antibodies, with more advantages over the latter (Figure 2). Its generation using cell-free chemical synthesis are comparatively (i) cheaper in production cost on the weight scale, (ii) less variability between batches with better control over post-production modification, (iii) less immunogenic, and (iv) miniature in size (5). These unique assets of aptamers may ultimately alter the animal-based antibody market, worldwide, given the increasing global demand for research antibodies, as per highlighted in an industry report on Research Antibodies Market Size & Share, 2018-2025. The potential market is huge, not limited only to diagnostics-based aptamer products but also for medical treatment purposes such as bacterial and viral treatment, cancer immunotherapy, antitoxins or drug design.  Furthermore, the ever-increasing market demand for cost-effective treatments, automated advancements in synthesis and formulation, and the expiration of the research patent, convey a strong stimulant for promising class of therapeutics’ evolution (6). At the moment, aptamers may not be a total replacement of antibodies, but they are definitely gaining traction as an attractive solution where antibodies’ efficiency is limited. We believe the greener future in science in already here wait for us to unlock the endless possibility.



1. Sun, H., Zhu, X., Lu, P. Y., Rosato, R. R., Tan, W., & Zu, Y. (2014). Oligonucleotide aptamers: new tools for targeted cancer therapy. Molecular therapy. Nucleic acids, 3(8), e182. https://doi.org/10.1038/mtna.2014.32
2. Strehlitz, B., Reinemann, C., Linkorn, S., & Stoltenburg, R. (2012). Aptamers for pharmaceuticals and their application in environmental analytics. Bioanalytical reviews, 4(1), 1–30. doi:10.1007/s12566-011-0026-1.
3. McKeague, M., De Girolamo, A., Valenzano, S., Pascale, M., Ruscito, A., Velu, R., Frost, N. R., Hill, K., Smith, M., McConnell, E. M. & DeRosa, M. C. (2015). Comprehensive Analytical Comparison of Strategies Used for Small Molecule Aptamer Evaluation. Analytical Chemistry, 87 (17), 8608-8612. dOI: 10.1021/acs.analchem.5b02102.
4. Thiviyanathan, V., & Gorenstein, D. G. (2012). Aptamers and the next generation of diagnostic reagents. Proteomics. Clinical applications, 6(11-12), 563–573. https://doi.org/10.1002/prca.201200042.

5. Kaur, H., Bruno, J.G., Kumar, A. & Sharma, T.K. (2018). Aptamers in the Therapeutics and Diagnostics Pipelines. Theranostics, 8(15), 4016-4032. doi:10.7150/thno.25958.
6. Zhou, J., & Rossi, J. (2017). Aptamers as targeted therapeutics: current potential and challenges. Nature reviews. Drug discovery, 16(3), 181–202. https://doi.org/10.1038/nrd.2016.199.