Aptamer

Left: Unbound aptamer. Right: the aptamer bound to its target protein. The protein is in yellow. Parts of the aptamer that change shape when it binds its target are in blue, while the unchanging parts are in orange. The parts of the aptamer that contact the protein are highlighted in red.
Breast cancer cells incubated with aptamers that bind selectively to biomarkers on the cancer cells, but not to healthy cells. Aptamers are linked to Alexa Fluor 594, a molecule that glows red under UV light. This type of test allows a doctor or researcher to identify cancer cells in a tissue sample from a patient.

Aptamers are oligomers of artificial ssDNA, RNA, XNA, or peptide that bind a specific target molecule, or family of target molecules. They exhibit a range of affinities (KD in the pM to μM range),[1][2] with variable levels of off-target binding[3] and are sometimes classified as chemical antibodies. Aptamers and antibodies can be used in many of the same applications, but the nucleic acid-based structure of aptamers, which are mostly oligonucleotides, is very different from the amino acid-based structure of antibodies, which are proteins. This difference can make aptamers a better choice than antibodies for some purposes (see antibody replacement).

Aptamers are used in biological lab research and medical tests. If multiple aptamers are combined into a single assay, they can measure large numbers of different proteins in a sample. They can be used to identify molecular markers of disease, or can function as drugs, drug delivery systems and controlled drug release systems. They also find use in other molecular engineering tasks.

Most aptamers originate from SELEX, a family of test-tube experiments for finding useful aptamers in a massive pool of different DNA sequences. This process is much like natural selection, directed evolution or artificial selection. In SELEX, the researcher repeatedly selects for the best aptamers from a starting DNA library made of about a quadrillion different randomly generated pieces of DNA or RNA. After SELEX, the researcher might mutate or change the chemistry of the aptamers and do another selection, or might use rational design processes to engineer improvements. Non-SELEX methods for discovering aptamers also exist.

Researchers optimize aptamers to achieve a variety of beneficial features. The most important feature is specific and sensitive binding to the chosen target. When aptamers are exposed to bodily fluids, as in serum tests or aptamer therapeutics, it is often important for them to resist digestion by DNA- and RNA-destroying proteins. Therapeutic aptamers often must be modified to clear slowly from the body. Aptamers that change their shape dramatically when they bind their target are useful as molecular switches to turn a sensor on and off. Some aptamers are engineered to fit into a biosensor or in a test of a biological sample. It can be useful in some cases for the aptamer to accomplish a pre-defined level or speed of binding. As the yield of the synthesis used to produce known aptamers shrinks quickly for longer sequences,[4] researchers often truncate aptamers to the minimal binding sequence to reduce the production cost.

  1. ^ Rhodes, Andrew; Smithers, Nick; Chapman, Trevor; Parsons, Sarah; Rees, Stephen (2001-10-05). "The generation and characterisation of antagonist RNA aptamers to MCP-1". FEBS Letters. 506 (2): 85–90. doi:10.1016/S0014-5793(01)02895-2. ISSN 0014-5793. PMID 11591377. S2CID 36797240.
  2. ^ Stoltenburg, Regina; Nikolaus, Nadia; Strehlitz, Beate (2012-12-30). "Capture-SELEX: Selection of DNA Aptamers for Aminoglycoside Antibiotics". Journal of Analytical Methods in Chemistry. 2012: e415697. doi:10.1155/2012/415697. ISSN 2090-8865. PMC 3544269. PMID 23326761.
  3. ^ Crivianu-Gaita V, Thompson M (November 2016). "Aptamers, antibody scFv, and antibody Fab' fragments: An overview and comparison of three of the most versatile biosensor biorecognition elements". Biosensors & Bioelectronics. 85: 32–45. doi:10.1016/j.bios.2016.04.091. PMID 27155114.
  4. ^ "DNA Oligonucleotide Synthesis". Millipore Sigma. Retrieved 4 July 2022.