Aptamers vs. Antibodies

It has been widely exploited that DNA and RNA can interact with other nucleic acids in transcription and DNA replication. Recent studies unveil that strong interactions between DNA and RNA oligonucleotides and other types of molecules, such as metal ions, small molecules, and large macromolecules, are also existing. These DNA and RNA oligonucleotides are called aptamers, also defined as artificial antibodies due to the capability of binding to a pre-determined target with high affinity and specificity.

Introduction to Aptamers

The term aptamer is derived from two Latin terms, aptus, meaning 'to fit', and meros meaning 'part'. Aptamers are single-stranded and short nucleic acids (DNA or RNA) that fold into complex structures. Researchers define aptamers as artificial antibodies for two reasons. On the one hand, aptamers are generated from a pool of random sequence oligonucleotides containing about 1015 different sequences with means of iterative in vitro selection alternating binding and amplification steps. On the other hand, they can fit and selectively bind to a target of interest, like proteins, peptides, carbohydrates, small molecules, toxins, and live cells.

In Vitro Selection of Aptamers

The development and advancement of aptamers are greatly attributed to the SELEX (systematic evolution of ligands by exponential enrichment) tool. The selection of aptamers is on the condition of mixing the target with a single-stranded DNA library. The first stage will keep oligonucleotides that bind to the target and the rest free sequences will be washed away by a series of filtration, chromatography, and centrifugation.

Then the retained target-bound oligonucleotides will be amplified by PCR (the polymerase chain reaction) to increase the concentration of sequences, which will be repeated several times under increased selection pressure and more strict binding conditions. As a result, only sequences that bind strongly to the target can survive in the process of SELEX selection and then be identified as aptamers by sequencing.

The in vitro selection process has created aptamers for over 100 proteins, including growth factors, transcription factors, enzymes, and immunoglobulins. However, successful aptamer therapeutics are required to be highly stable with moderate length and good pharmacokinetics, which can be achieved by further aptamer characterization and evaluation.

Compared Aptamers with Antibodies

Similar to antibodies, aptamers can specifically bind to targets to regulate or block biological activities.

Though aptamers are synthetic antibodies, they outperform natural antibodies from many aspects in practice. Aptamers can be created in vitro and come into effect against almost any kind of targets, including toxic or non-immunogenic targets, while antibodies are completely dependent on immune responses. The smaller size of aptamers helps them bind to targets and penetrate tissues with more affinity and higher specificity, and additionally decides that aptamers can be chemically modified in a defined and precise way.

When it comes to storage and delivery, aptamers have advantages over antibodies as well in that aptamers are reversible when denatured and more stable at room temperature, while antibodies are restrictively temperature-sensitive with limited shelf life and require refrigeration in storage and transportation.

Applications of Aptamers

The applications are extremely versatile, including aptamer research agents or therapeutics, aptamers for diagnostics in human and animal health, aptamer-based biosensors, and aptamer tools for biomarker or drug discovery.

With several ongoing clinical trials, aptamers are anticipated to be therapeutic agents and drug-delivery agents in the form of aptamer conjugations. Aptamers can serve as antagonists that prevent specific receptor-ligand interactions or as agonists that bind to a receptor to activate signals because these synthetic antibodies are easy to be addressed to intracellular targets, membrane components, and circulating molecules.

Aptamers can bind to non–immunogenic and toxic targets, which allows them to be used in vivo. Therefore, aptamers are ideal point-of-care diagnostic tools in human and animal health due to their ability to specifically bind to biomarkers. And aptamer fluorescent and radio-labeled probes can be applied in imaging tumor tissues. Besides, aptamers can be used for the purposes of analytics as well as environment and food safety monitoring since they can be selected and employed in non-physiological conditions.

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