Aptamer

Aptamer Overview:
– Etymology and Classification:
– Term ‘aptamer’ coined by Andrew Ellington and Jack Szostak.
– Derived from Greek words meaning ‘to connect or fit.’
– Neologism used to describe individual RNA sequences.
– Latin root ‘aptus’ meaning ‘to fit.’
– Greek roots ‘ἅπτω’ and ‘μέρος’ signify fitting components.
– Aptamers are synthetically generated ligands.
– Exploit diversity of DNA, RNA, XNA, or peptide.
– Achieve strong, specific binding for target molecules.
– Sometimes classified as chemical antibodies or antibody mimics.
– Smaller in size (6-30 kDa) compared to antibodies.

Aptamer Properties and Applications:
– Properties and Structure:
– Aptamers have complex secondary and tertiary structures.
– Complementary base pairing enhances stability.
– Chemical modifications improve durability and function.
– Different chemistries offer distinct profiles.
– DNA- and RNA-based aptamers exhibit low immunogenicity.
– Applications:
– Used in biological lab research and medical tests.
– Can measure large numbers of different proteins in a sample.
– Identify molecular markers of disease.
– Function as drugs, drug delivery systems, and controlled release systems.
– Useful in molecular engineering tasks and biosensors.

Aptamer Targets and Interactions:
– Target Variety:
– Aptamer targets include small molecules, heavy metal ions, proteins, and whole cells.
– Specific targets include lysozyme, thrombin, HIV TAR, hemin, interferon γ, VEGF, PSA, dopamine, and HSF1.
– Aptamers developed against cancer cells, prions, bacteria, and various viruses.
– Interactions with Proteins:
– Aptamers show high affinity for specific proteins.
– Used in biosensors and electrochemical sensors for protein detection.
– Understanding structure-based interactions crucial for predicting binding accuracy.
– Offer potential for enhanced predictability of aptamer-protein interactions.
– Improved 3-D structural predictions can reduce the need for experimental SELEX protocol.

Aptamer Applications and Advancements:
– Therapeutic and Diagnostic Applications:
– Aptamers used as diagnostic tools in clinical applications.
– Detect viral infections, sense biomolecules, monitor protein levels, and improve diagnostic accuracy.
– Potential therapeutics, targeted drug delivery, neuro-oncology, and novel therapeutic agents.
– Advancements in Technology:
– Split aptamers for biosensors, molecular imaging, and nanomaterial-based aptasensors.
– Enhanced protein binding affinities, colorimetric sensing of proteins, and chromatographic purification of antibiotics.

Aptamer Selection Techniques and Future Perspectives:
– Selection Techniques:
– SELEX, high-throughput sequencing, Cell-SELEX, capillary electrophoresis-SELEX, and microfluidic-based SELEX.
– High binding affinity, specificity, stability, low immunogenicity, and ease of chemical modification.
– Future Perspectives:
– Challenges and opportunities in aptamer development.
– Predictions for the future of aptamer-based diagnostics and therapeutics.
– Potential of aptamers as versatile molecular tools and re-evaluating conventional wisdom about binding assays.

Aptamer (Wikipedia)

Aptamers are short sequences of artificial DNA, RNA, XNA, or peptide that bind a specific target molecule, or family of target molecules. They exhibit a range of affinities (K_D in the pM to μM range), with variable levels of off-target binding 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, researchers often truncate aptamers to the minimal binding sequence to reduce the production cost.