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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 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 (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.


The word "aptamer" is a neologism coined by Andrew Ellington and Jack Szostak in their first publication on the topic. They did not provide a precise definition, stating "We have termed these individual RNA sequences 'aptamers', from the Latin 'aptus', to fit."[5]

The word itself, however, derives from the Greek word ἅπτω, to connect or fit (as used by Homer (c. 8th century BC)[6] [7]) and μέρος, a component of something larger.[8]


A typical aptamer is a synthetically generated ligand exploiting the combinatorial diversity of DNA, RNA, XNA, or peptide to achieve strong, specific binding for a particular target molecule or family of target molecules. Aptamers are occasionally classified as "chemical antibodies" or "antibody mimics".[9] However, most aptamers are small, with a molecular weight of 6-30 kDa, in contrast to the 150 kDa size of antibodies, and contain one binding site rather than the two matching antigen binding regions of a typical antibody.


Jack Szostak, Nobel laureate and one of the inventors of SELEX and aptamers.

Since its first application in 1967,[10] directed evolution methodologies have been used to develop biomolecules with new properties and functions. Early examples include the modification of the bacteriophage Qbeta replication system and the generation of ribozymes with modified cleavage activity.[11]

In 1990, two teams independently developed and published SELEX (Systematic Evolution of Ligands by EXponential enrichment) methods and generated RNA aptamers: the lab of Larry Gold, using the term SELEX for their process of selecting RNA ligands against T4 DNA polymerase[12] and the lab of Jack Szostak, selecting RNA ligands against various organic dyes.[5][13] Two years later, the Szostak lab and Gilead Sciences, acting independently of one another, used in vitro selection schemes to generate DNA aptamers for organic dyes[14] and human thrombin,[15] respectively. In 2001, SELEX was automated by J. Colin Cox in the Ellington lab, reducing the duration of a weeks-long selection experiment to just three days.[16][17][18]

In 2002, two groups led by Ronald Breaker and Evgeny Nudler published the first definitive evidence for a riboswitch, a nucleic acid-based genetic regulatory element, the existence of which had previously been suspected. Riboswitches possess similar molecular recognition properties to aptamers. This discovery added support to the RNA World hypothesis, a postulated stage in time in the origin of life on Earth.[19]



The complex and diverse secondary and tertiary structure of aptamers, as shown in this schematic of an aptamer's secondary structure, is what lets them bind their target strongly and specifically. Complementary base pairing is visible in the black lines connecting some G-C and A-T bases. This is a feature of nucleic acids that does not exist in the amino acids of antibodies. It helps aptamers form these unique structures. Hairpin regions (red), which rely on this base pairing, enhance the aptamer's stability at different temperatures. This image also shows examples of chemical modifications to the base aptamer. Two unnatural bases, which enhance durability, are in yellow. The biotin molecule binds with extreme strength to streptavidin, allowing the aptamer to be anchored to other molecules or to a surface in sensors and assays.

Most aptamers are based on a specific oligomer sequence of 20-100 bases and 3-20 kDa. Some have chemical modifications for functional enhancements or compatibility with larger engineered molecular systems. DNA, RNA, XNA, and peptide aptamer chemistries can each offer distinct profiles in terms of shelf stability, durability in serum or in vivo, specificity and sensitivity, cost, ease of generation, amplification, and characterization, and familiarity to users. Typically, DNA- and RNA-based aptamers exhibit low immunogenicity, are amplifiable via Polymerase Chain Reaction (PCR), and have complex secondary structure and tertiary structure.[20][21][22][23] DNA- and XNA-based aptamers exhibit superior shelf stability. XNA-based aptamers can introduce additional chemical diversity to increase binding affinity or greater durability in serum or in vivo.

As 22 genetically-encoded and over 500 naturally-occurring amino acids exist, peptide aptamers, as well as antibodies, have much greater potential combinatorial diversity per unit length relative to the 4 nucleic acids in DNA or RNA.[24] Chemical modifications of nucleic acid bases or backbones increase the chemical diversity of standard nucleic acid bases.[25]

Split aptamers are composed of two or more DNA strands that are pieces of a larger parent aptamer that has been broken in two by a molecular nick.[26] The ability of each component strand to bind targets will depend on the location of the nick, as well as the secondary structures of the daughter strands.[27] The presence of a target molecule supports the joining of DNA fragments. This can be used as the basis for biosensors.[28] Once assembled, the two separate DNA strands can be ligated into a single strand.

Unmodified aptamers are cleared rapidly from the bloodstream, with a half-life of seconds to hours. This is mainly due to nuclease degradation, which physically destroys the aptamers, as well as clearance by the kidneys, a result of the aptamer's low molecular weight and size. Several modifications, such as 2'-fluorine-substituted pyrimidines and polyethylene glycol (PEG) linkage, permit a serum half-life of days to weeks. PEGylation can add sufficient mass and size to prevent clearance by the kidneys in vivo. Unmodified aptamers can treat coagulation disorders. The problem of clearance and nuclease digestion is diminished when they are applied to the eye, where there is a lower concentration of nuclease and the rate of clearance is lower.[29] Rapid clearance from serum can also be useful in some applications, such as in vivo diagnostic imaging.[30]

In a study on aptamers[31] designed to bind with proteins associated with Ebola infection, a comparison was made among three aptamers isolated for their ability to bind the target protein EBOV sGP. Although these aptamers vary in both sequence and structure, they exhibit remarkably similar relative affinities for sGP from EBOV and SUDV, as well as EBOV GP1.2. Notably, these aptamers demonstrated a high degree of specificity for the GP gene products. One aptamer, in particular, proved effective as a recognition element in an electrochemical sensor, enabling the detection of sGP and GP1.2 in solution, as well as GP1.2 within a membrane context.The results of this research point to the intriguing possibility that certain regions on protein surfaces may possess aptatropic qualities. Identifying the key features of such sites, in conjunction with improved 3-D structural predictions for aptamers, holds the potential to enhance the accuracy of predicting aptamer interaction sites on proteins. This, in turn, may help identify aptamers with a heightened likelihood of binding proteins with high affinity, as well as shed light on protein mutations that could significantly impact aptamer binding.This comprehensive understanding of the structure-based interactions between aptamers and proteins is vital for refining the computational predictability of aptamer-protein binding. Moreover, it has the potential to eventually eliminate the need for the experimental SELEX protocol.


Aptamer targets can include small molecules and heavy metal ions, larger ligands such as proteins, and even whole cells.[32][33] These targets include lysozyme,[34] thrombin,[35][36] human immunodeficiency virus trans-acting responsive element (HIV TAR),[37] hemin,[38] interferon γ,[39] vascular endothelial growth factor (VEGF),[40][41] prostate specific antigen (PSA),[42][43] dopamine,[44] and the non-classical oncogene, heat shock factor 1 (HSF1).[45]

Aptamers have been generated against cancer cells,[46] prions,[47] bacteria,[48] and viruses. Viral targets of aptamers include influenza A and B viruses,[49] Respiratory syncytial virus (RSV),[49] SARS coronavirus (SARS-CoV)[49] and SARS-CoV-2.[50]

Aptamers may be particularly useful for environmental science proteomics.[51] Antibodies, like other proteins, are more difficult to sequence than nucleic acids. They are also costly to maintain and produce, and are at constant risk of contamination, as they are produced via cell culture or are harvested from animal serum. For this reason, researchers interested in little-studied proteins and species may find that companies will not produce, maintain, or adequately validate the quality of antibodies against their target of interest.[52] By contrast, aptamers are simple to sequence and cost nothing to maintain, as their exact structure can be stored digitally and synthesized on demand. This may make them more economically feasible as research tools for underfunded biological research subjects. Aptamers exist for plant compounds, such as theophylline (found in tea)[53] and abscisic acid (a plant immune hormone).[54] An aptamer against a-amanitin (the toxin that causes lethal Amanita poisoning) has been developed, an example of an aptamer against a mushroom target.[55]

Aptamer applications can be roughly grouped into sensing, therapeutic, reagent production, and engineering categories. Sensing applications are important in environmental, biomedical, epidemiological, biosecurity, and basic research applications, where aptamers act as probes in assays, imaging methods, diagnostic assays, and biosensors.[32][56][57][58][59][60] In therapeutic applications and precision medicine, aptamers can function as drugs,[61] as targeted drug delivery vehicles,[62] as controlled release mechanisms, and as reagents for drug discovery via high-throughput screening for small molecules[63] and proteins.[64][65] Aptamers have application for protein production monitoring, quality control, and purification.[66][67][68] They can function in molecular engineering applications as a way to modify proteins, such as enhancing DNA polymerase to make PCR more reliable.[69][70][71][72]

Because the affinity of the aptamer also affects its dynamic range and limit of detection, aptamers with a lower affinity may be desirable when assaying high concentrations of a target molecule.[73] Affinity chromatography also depends on the ability of the affinity reagent, such as an aptamer, to bind and release its target, and lower affinities may aid in the release of the target molecule.[74] Hence, specific applications determine the useful range for aptamer affinity.

Antibody replacement[edit]

Aptamers can replace antibodies in many biotechnology applications.[75][52] In laboratory research and clinical diagnostics, they can be used in aptamer-based versions of immunoassays including enzyme-linked immunosorbent assay (ELISA),[76] western blot,[77] immunohistochemistry (IHC),[78] and flow cytometry.[79] As therapeutics, they can function as agonists or antagonists of their ligand.[80] While antibodies are a familiar technology with a well-developed market, aptamers are a relatively new technology to most researchers, and aptamers have been generated against only a fraction of important research targets.[81] Unlike antibodies, unmodified aptamers are more susceptible to nuclease digestion in serum and renal clearance in vivo. Aptamers are much smaller in size and mass than antibodies, which could be a relevant factor in choosing which is best suited for a given application. When aptamers are available for a particular application, their advantages over antibodies include potentially lower immunogenicity, greater replicability and lower cost, a greater level of control due to the in vitro selection conditions, and capacity to be efficiently engineered for durability, specificity, and sensitivity.[82]

In addition, aptamers contribute to reduction of research animal use.[83] While antibodies often rely on animals for initial discovery, as well as for production in the case of polyclonal antibodies, both the selection and production of aptamers is typically animal-free. However, phage display methods allow for selection of antibodies in vitro, followed by production from a monoclonal cell line, avoiding the use of animals entirely.[84]

Controlled release of therapeutics[edit]

The ability of aptamers to reversibly bind molecules such as proteins has generated increasing interest in using them to facilitate controlled release of therapeutic biomolecules, such as growth factors. This can be accomplished by tuning the binding strength to passively release the growth factors,[85] along with active release via mechanisms such as hybridization of the aptamer with complementary oligonucleotides[86] or unfolding of the aptamer due to cellular traction forces.[87]


AptaBiD (Aptamer-Facilitated Biomarker Discovery) is an aptamer-based method for biomarker discovery.[88]

Peptide Aptamers[edit]

While most aptamers are based on DNA, RNA, or XNA, peptide aptamers[89] are artificial proteins selected or engineered to bind specific target molecules.


Peptide aptamers consist of one or more peptide loops of variable sequence displayed by a protein scaffold. Derivatives known as tadpoles, in which peptide aptamer "heads" are covalently linked to unique sequence double-stranded DNA "tails", allow quantification of scarce target molecules in mixtures by PCR (using, for example, the quantitative real-time polymerase chain reaction) of their DNA tails.[90] The peptides that form the aptamer variable regions are synthesized as part of the same polypeptide chain as the scaffold and are constrained at their N and C termini by linkage to it. This double structural constraint decreases the diversity of the 3D structures that the variable regions can adopt,[91] and this reduction in structural diversity lowers the entropic cost of molecular binding when interaction with the target causes the variable regions to adopt a uniform structure.


The most common peptide aptamer selection system is the yeast two-hybrid system. Peptide aptamers can also be selected from combinatorial peptide libraries constructed by phage display and other surface display technologies such as mRNA display, ribosome display, bacterial display and yeast display. These experimental procedures are also known as biopanning. All the peptides panned from combinatorial peptide libraries have been stored in the MimoDB database.[92][93]


Libraries of peptide aptamers have been used as "mutagens", in studies in which an investigator introduces a library that expresses different peptide aptamers into a cell population, selects for a desired phenotype, and identifies those aptamers that cause the phenotype. The investigator then uses those aptamers as baits, for example in yeast two-hybrid screens to identify the cellular proteins targeted by those aptamers. Such experiments identify particular proteins bound by the aptamers, and protein interactions that the aptamers disrupt, to cause the phenotype.[94][95] In addition, peptide aptamers derivatized with appropriate functional moieties can cause specific post-translational modification of their target proteins, or change the subcellular localization of the targets.[96]

This assay tests the ability of two different types of aptamers (V and I) to detect their respective protein targets (VEGF and IFN-y). The labels Apt1, Apt2, Apt3, and Apt4 are in decreasing order of binding strength (i.e. Apt1 is the strongest aptamer). The DD, AD, DA, and AA letters mean that they have different combinations of unnatural base pairs. This causes their difference in binding strengths. The "-" columns have no protein, and the "+" columns do have protein. Aptamer with protein (+) and without protein (-) is loaded into wells in a gel and moves down the column lanes. If target is present, they bind and travel more slowly, due to the charge on the aptamer and the mass of the protein. Otherwise, the unbound aptamer moves quickly to the end of the lane. The difference in position between the "+" and "-" bands is the "mobility shift." This allows the researcher to detect the presence or absence of the protein. The darker band in the leftmost V and I lanes show that stronger aptamer-target binding makes it easier to detect the target at a given amount of target protein in the sample. The bottom image includes denaturing urea in the gel that disrupts aptamer-target binding in the weaker I aptamers, showing that the aptamer-protein binding is indeed what caused the mobility shift.

Industry and Research Community[edit]

Commercial products and companies based on aptamers include the drug Macugen (pegaptanib)[97] and the clinical diagnostic company SomaLogic.[98] The International Society on Aptamers (INSOAP), a professional society for the aptamer research community, publishes a journal devoted to the topic, Aptamers. Apta-index[99] is a current database cataloging and simplifying the ordering process for over 700 aptamers.

See also[edit]


  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.
  5. ^ a b Ellington AD, Szostak JW (August 1990). "In vitro selection of RNA molecules that bind specific ligands". Nature. 346 (6287): 818–822. Bibcode:1990Natur.346..818E. doi:10.1038/346818a0. PMID 1697402. S2CID 4273647.
  6. ^ "ἅπτω", Βικιλεξικό (in Greek), 2023-03-12, retrieved 2024-03-21
  7. ^ "Οδύσσεια/φ - Βικιθήκη". el.wikisource.org (in Greek). Retrieved 2024-03-21.
  8. ^ "μέρος", Wiktionary, the free dictionary, 2023-05-31, retrieved 2024-03-21
  9. ^ Zhou G, Wilson G, Hebbard L, Duan W, Liddle C, George J, Qiao L (March 2016). "Aptamers: A promising chemical antibody for cancer therapy". Oncotarget. 7 (12): 13446–13463. doi:10.18632/oncotarget.7178. PMC 4924653. PMID 26863567. S2CID 16618423.
  10. ^ Mills DR, Peterson RL, Spiegelman S (July 1967). "An extracellular Darwinian experiment with a self-duplicating nucleic acid molecule". Proceedings of the National Academy of Sciences of the United States of America. 58 (1): 217–224. Bibcode:1967PNAS...58..217M. doi:10.1073/pnas.58.1.217. PMC 335620. PMID 5231602.
  11. ^ Joyce GF (October 1989). "Amplification, mutation and selection of catalytic RNA". Gene. 82 (1): 83–87. doi:10.1016/0378-1119(89)90033-4. PMID 2684778.
  12. ^ Tuerk C, Gold L (August 1990). "Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase". Science. 249 (4968): 505–510. Bibcode:1990Sci...249..505T. doi:10.1126/science.2200121. PMID 2200121.
  13. ^ Stoltenburg R, Reinemann C, Strehlitz B (October 2007). "SELEX--a (r)evolutionary method to generate high-affinity nucleic acid ligands". Biomolecular Engineering. 24 (4): 381–403. doi:10.1016/j.bioeng.2007.06.001. PMID 17627883.
  14. ^ Ellington AD, Szostak JW (February 1992). "Selection in vitro of single-stranded DNA molecules that fold into specific ligand-binding structures". Nature. 355 (6363): 850–852. Bibcode:1992Natur.355..850E. doi:10.1038/355850a0. PMID 1538766. S2CID 4332485.
  15. ^ Bock LC, Griffin LC, Latham JA, Vermaas EH, Toole JJ (February 1992). "Selection of single-stranded DNA molecules that bind and inhibit human thrombin". Nature. 355 (6360): 564–566. Bibcode:1992Natur.355..564B. doi:10.1038/355564a0. PMID 1741036. S2CID 4349607.
  16. ^ Cox JC, Ellington AD (October 2001). "Automated selection of anti-protein aptamers". Bioorganic & Medicinal Chemistry. 9 (10): 2525–2531. doi:10.1016/s0968-0896(01)00028-1. PMID 11557339.
  17. ^ Cox JC, Rajendran M, Riedel T, Davidson EA, Sooter LJ, Bayer TS, et al. (June 2002). "Automated acquisition of aptamer sequences". Combinatorial Chemistry & High Throughput Screening. 5 (4): 289–299. doi:10.2174/1386207023330291. PMID 12052180.
  18. ^ Cox JC, Hayhurst A, Hesselberth J, Bayer TS, Georgiou G, Ellington AD (October 2002). "Automated selection of aptamers against protein targets translated in vitro: from gene to aptamer". Nucleic Acids Research. 30 (20): 108e–108. doi:10.1093/nar/gnf107. PMC 137152. PMID 12384610.
  19. ^ Breaker RR (February 2012). "Riboswitches and the RNA world". Cold Spring Harbor Perspectives in Biology. 4 (2): a003566. doi:10.1101/cshperspect.a003566. PMC 3281570. PMID 21106649.
  20. ^ Svigelj R, Dossi N, Toniolo R, Miranda-Castro R, de-Los-Santos-Álvarez N, Lobo-Castañón MJ (September 2018). "Selection of Anti-gluten DNA Aptamers in a Deep Eutectic Solvent". Angewandte Chemie. 57 (39): 12850–12854. Bibcode:2018AngCh.13013032S. doi:10.1002/ange.201804860. hdl:10651/49996. PMID 30070419. S2CID 240281828.
  21. ^ Neves MA, Reinstein O, Saad M, Johnson PE (December 2010). "Defining the secondary structural requirements of a cocaine-binding aptamer by a thermodynamic and mutation study". Biophysical Chemistry. 153 (1): 9–16. doi:10.1016/j.bpc.2010.09.009. PMID 21035241.
  22. ^ Baugh C, Grate D, Wilson C (August 2000). "2.8 A crystal structure of the malachite green aptamer". Journal of Molecular Biology. 301 (1): 117–128. doi:10.1006/jmbi.2000.3951. PMID 10926496.
  23. ^ Dieckmann T, Fujikawa E, Xhao X, Szostak J, Feigon J (1995). "Structural Investigations of RNA and DNA aptamers in Solution". Journal of Cellular Biochemistry. 59: 13–81. doi:10.1002/jcb.240590703. S2CID 221833821.
  24. ^ Mascini M, Palchetti I, Tombelli S (February 2012). "Nucleic acid and peptide aptamers: fundamentals and bioanalytical aspects". Angewandte Chemie. 51 (6): 1316–1332. doi:10.1002/anie.201006630. PMID 22213382.
  25. ^ Lipi F, Chen S, Chakravarthy M, Rakesh S, Veedu RN (December 2016). "In vitro evolution of chemically-modified nucleic acid aptamers: Pros and cons, and comprehensive selection strategies". RNA Biology. 13 (12): 1232–1245. doi:10.1080/15476286.2016.1236173. PMC 5207382. PMID 27715478.
  26. ^ Chen A, Yan M, Yang S (2016). "Split aptamers and their applications in sandwich aptasensors". TrAC Trends in Analytical Chemistry. 80: 581–593. doi:10.1016/j.trac.2016.04.006.
  27. ^ Kent AD, Spiropulos NG, Heemstra JM (October 2013). "General approach for engineering small-molecule-binding DNA split aptamers". Analytical Chemistry. 85 (20): 9916–9923. doi:10.1021/ac402500n. PMID 24033257.
  28. ^ Debiais M, Lelievre A, Smietana M, Müller S (April 2020). "Splitting aptamers and nucleic acid enzymes for the development of advanced biosensors". Nucleic Acids Research. 48 (7): 3400–3422. doi:10.1093/nar/gkaa132. PMC 7144939. PMID 32112111.
  29. ^ Drolet DW, Green LS, Gold L, Janjic N (June 2016). "Fit for the Eye: Aptamers in Ocular Disorders". Nucleic Acid Therapeutics. 26 (3): 127–146. doi:10.1089/nat.2015.0573. PMC 4900223. PMID 26757406.
  30. ^ Wang AZ, Farokhzad OC (March 2014). "Current progress of aptamer-based molecular imaging". Journal of Nuclear Medicine. 55 (3): 353–356. doi:10.2967/jnumed.113.126144. PMC 4110511. PMID 24525205.
  31. ^ Banerjee, S.; Hemmat, M.A.; Shubham, S.; Gosai, A.; Devarakonda, S.; Jiang, N.; Geekiyanage, C.; Dillard, J.A.; Maury, W.; Shrotriya, P.; et al. Structurally Different Yet Functionally Similar: Aptamers Specific for the Ebola Virus Soluble Glycoprotein and GP1,2 and Their Application in Electrochemical Sensing. Int. J. Mol. Sci. 2023, 24, 4627. https://doi.org/10.3390/ijms24054627
  32. ^ a b Kaur H, Shorie M (June 2019). "Nanomaterial based aptasensors for clinical and environmental diagnostic applications". Nanoscale Advances. 1 (6): 2123–2138. Bibcode:2019NanoA...1.2123K. doi:10.1039/C9NA00153K. PMC 9418768. PMID 36131986.
  33. ^ Mallikaratchy P (January 2017). "Evolution of Complex Target SELEX to Identify Aptamers against Mammalian Cell-Surface Antigens". Molecules. 22 (2): 215. doi:10.3390/molecules22020215. PMC 5572134. PMID 28146093.
  34. ^ Potty AS, Kourentzi K, Fang H, Jackson GW, Zhang X, Legge GB, Willson RC (February 2009). "Biophysical characterization of DNA aptamer interactions with vascular endothelial growth factor". Biopolymers. 91 (2): 145–156. doi:10.1002/bip.21097. PMID 19025993. S2CID 23670.
  35. ^ Long SB, Long MB, White RR, Sullenger BA (December 2008). "Crystal structure of an RNA aptamer bound to thrombin". RNA. 14 (12): 2504–2512. doi:10.1261/rna.1239308. PMC 2590953. PMID 18971322.
  36. ^ Kohn, Eric M.; Konovalov, Kirill; Gomez, Christian A.; Hoover, Gillian N.; Yik, Andrew Kai-hei; Huang, Xuhui; Martell, Jeffrey D. (2023-08-02). "Terminal Alkyne-Modified DNA Aptamers with Enhanced Protein Binding Affinities". ACS Chemical Biology. 18 (9): 1976–1984. doi:10.1021/acschembio.3c00183. ISSN 1554-8929. PMID 37531184.
  37. ^ Darfeuille F, Reigadas S, Hansen JB, Orum H, Di Primo C, Toulmé JJ (October 2006). "Aptamers targeted to an RNA hairpin show improved specificity compared to that of complementary oligonucleotides". Biochemistry. 45 (39): 12076–12082. doi:10.1021/bi0606344. PMID 17002307.
  38. ^ Liu M, Kagahara T, Abe H, Ito Y (2009). "Direct In Vitro Selection of Hemin-Binding DNA Aptamer with Peroxidase Activity". Bulletin of the Chemical Society of Japan. 82: 99–104. doi:10.1246/bcsj.82.99.
  39. ^ Min K, Cho M, Han SY, Shim YB, Ku J, Ban C (July 2008). "A simple and direct electrochemical detection of interferon-gamma using its RNA and DNA aptamers". Biosensors & Bioelectronics. 23 (12): 1819–1824. doi:10.1016/j.bios.2008.02.021. PMID 18406597.
  40. ^ Ng EW, Shima DT, Calias P, Cunningham ET, Guyer DR, Adamis AP (February 2006). "Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease". Nature Reviews. Drug Discovery. 5 (2): 123–132. doi:10.1038/nrd1955. PMID 16518379. S2CID 8833436.
  41. ^ Moghadam, Fatemeh Mortazavi; Rahaie, Mahdi (May 2019). "A signal-on nanobiosensor for VEGF165 detection based on supraparticle copper nanoclusters formed on bivalent aptamer". Biosensors and Bioelectronics. 132: 186–195. doi:10.1016/j.bios.2019.02.046. PMID 30875630. S2CID 80613434.
  42. ^ Savory N, Abe K, Sode K, Ikebukuro K (December 2010). "Selection of DNA aptamer against prostate specific antigen using a genetic algorithm and application to sensing". Biosensors & Bioelectronics. 26 (4): 1386–1391. doi:10.1016/j.bios.2010.07.057. PMID 20692149.
  43. ^ Jeong S, Han SR, Lee YJ, Lee SW (March 2010). "Selection of RNA aptamers specific to active prostate-specific antigen". Biotechnology Letters. 32 (3): 379–385. doi:10.1007/s10529-009-0168-1. PMID 19943183. S2CID 22201181.
  44. ^ Walsh R, DeRosa MC (October 2009). "Retention of function in the DNA homolog of the RNA dopamine aptamer". Biochemical and Biophysical Research Communications. 388 (4): 732–735. doi:10.1016/j.bbrc.2009.08.084. PMID 19699181.
  45. ^ Salamanca HH, Antonyak MA, Cerione RA, Shi H, Lis JT (2014). "Inhibiting heat shock factor 1 in human cancer cells with a potent RNA aptamer". PLOS ONE. 9 (5): e96330. Bibcode:2014PLoSO...996330S. doi:10.1371/journal.pone.0096330. PMC 4011729. PMID 24800749.
  46. ^ Farokhzad OC, Karp JM, Langer R (May 2006). "Nanoparticle-aptamer bioconjugates for cancer targeting". Expert Opinion on Drug Delivery. 3 (3): 311–324. doi:10.1517/17425247.3.3.311. PMID 16640493. S2CID 37058942.
  47. ^ Proske D, Gilch S, Wopfner F, Schätzl HM, Winnacker EL, Famulok M (August 2002). "Prion-protein-specific aptamer reduces PrPSc formation". ChemBioChem. 3 (8): 717–725. doi:10.1002/1439-7633(20020802)3:8<717::AID-CBIC717>3.0.CO;2-C. PMID 12203970. S2CID 36801266.
  48. ^ Kaur H, Shorie M, Sharma M, Ganguli AK, Sabherwal P (December 2017). "Bridged Rebar Graphene functionalized aptasensor for pathogenic E. coli O78:K80:H11 detection". Biosensors & Bioelectronics. 98: 486–493. doi:10.1016/j.bios.2017.07.004. PMID 28728009.
  49. ^ a b c Asha K, Kumar P, Sanicas M, Meseko CA, Khanna M, Kumar B (December 2018). "Advancements in Nucleic Acid Based Therapeutics against Respiratory Viral Infections". Journal of Clinical Medicine. 8 (1): 6. doi:10.3390/jcm8010006. PMC 6351902. PMID 30577479.
  50. ^ Schmitz A, Weber A, Bayin M, Breuers S, Fieberg V, Famulok M, Mayer G (April 2021). "A SARS-CoV-2 Spike Binding DNA Aptamer that Inhibits Pseudovirus Infection by an RBD-Independent Mechanism*". Angewandte Chemie. 60 (18): 10279–10285. doi:10.1002/anie.202100316. PMC 8251191. PMID 33683787.
  51. ^ Dhar P, Samarasinghe RM, Shigdar S (April 2020). "Antibodies, Nanobodies, or Aptamers-Which Is Best for Deciphering the Proteomes of Non-Model Species?". International Journal of Molecular Sciences. 21 (7): 2485. doi:10.3390/ijms21072485. PMC 7177290. PMID 32260091.
  52. ^ a b Bauer M, Strom M, Hammond DS, Shigdar S (November 2019). "Anything You Can Do, I Can Do Better: Can Aptamers Replace Antibodies in Clinical Diagnostic Applications?". Molecules. 24 (23): 4377. doi:10.3390/molecules24234377. PMC 6930532. PMID 31801185.
  53. ^ Feng S, Chen C, Wang W, Que L (May 2018). "An aptamer nanopore-enabled microsensor for detection of theophylline". Biosensors & Bioelectronics. 105: 36–41. doi:10.1016/j.bios.2018.01.016. PMID 29351868.
  54. ^ Song C (2017). "Detection of plant hormone abscisic acid (ABA) using an optical aptamer-based sensor with a microfluidics capillary interface". 2017 IEEE 30th International Conference on Micro Electro Mechanical Systems (MEMS). pp. 370–373. doi:10.1109/MEMSYS.2017.7863418. ISBN 978-1-5090-5078-9. S2CID 20781208.
  55. ^ Muszyńska K, Ostrowska D, Bartnicki F, Kowalska E, Bodaszewska-Lubaś M, Hermanowicz P, et al. (2017). "Selection and analysis of a DNA aptamer binding α-amanitin from Amanita phalloides". Acta Biochimica Polonica. 64 (3): 401–406. doi:10.18388/abp.2017_1615. PMID 28787470. S2CID 3638299.
  56. ^ Penner G (July 2012). "Commercialization of an aptamer-based diagnostic test" (PDF). NeoVentures.
  57. ^ Wei H, Li B, Li J, Wang E, Dong S (September 2007). "Simple and sensitive aptamer-based colorimetric sensing of protein using unmodified gold nanoparticle probes". Chemical Communications (36): 3735–3737. doi:10.1039/B707642H. PMID 17851611.
  58. ^ Cheng H, Qiu X, Zhao X, Meng W, Huo D, Wei H (March 2016). "Functional Nucleic Acid Probe for Parallel Monitoring K(+) and Protoporphyrin IX in Living Organisms". Analytical Chemistry. 88 (5): 2937–2943. doi:10.1021/acs.analchem.5b04936. PMID 26866998.
  59. ^ Xiang Y, Lu Y (July 2011). "Using personal glucose meters and functional DNA sensors to quantify a variety of analytical targets". Nature Chemistry. 3 (9): 697–703. Bibcode:2011NatCh...3..697X. doi:10.1038/nchem.1092. PMC 3299819. PMID 21860458.
  60. ^ Agnivo Gosai, Brendan Shin Hau Yeah, Marit Nilsen-Hamilton, Pranav Shrotriya, "Label free thrombin detection in presence of high concentration of albumin using an aptamer-functionalized nanoporous membrane", Biosensors and Bioelectronics, Volume 126, 2019, pp. 88–95, ISSN 0956-5663, doi:10.1016/j.bios.2018.10.010.
  61. ^ Amero P, Khatua S, Rodriguez-Aguayo C, Lopez-Berestein G (October 2020). "Aptamers: Novel Therapeutics and Potential Role in Neuro-Oncology". Cancers. 12 (10): 2889. doi:10.3390/cancers12102889. PMC 7600320. PMID 33050158.
  62. ^ Fattal E, Hillaireau H, Ismail SI (September 2018). "Aptamers in Therapeutics and Drug Delivery". Advanced Drug Delivery Reviews. 134: 1–2. doi:10.1016/j.addr.2018.11.001. PMID 30442313. S2CID 53562925.
  63. ^ Hafner M, Vianini E, Albertoni B, Marchetti L, Grüne I, Gloeckner C, Famulok M (2008). "Displacement of protein-bound aptamers with small molecules screened by fluorescence polarization". Nature Protocols. 3 (4): 579–587. doi:10.1038/nprot.2008.15. PMID 18388939. S2CID 4997899.
  64. ^ Huang Z, Qiu L, Zhang T, Tan W (2021-02-03). "Integrating DNA Nanotechnology with Aptamers for Biological and Biomedical Applications". Matter. 4 (2): 461–489. doi:10.1016/j.matt.2020.11.002. ISSN 2590-2385. S2CID 234061584.
  65. ^ Reynaud L, Bouchet-Spinelli A, Raillon C, Buhot A (August 2020). "Sensing with Nanopores and Aptamers: A Way Forward". Sensors. 20 (16): 4495. Bibcode:2020Senso..20.4495R. doi:10.3390/s20164495. PMC 7472324. PMID 32796729.
  66. ^ Yang Y, Yin S, Li Y, Lu D, Zhang J, Sun C (2017). "Application of aptamers in detection and chromatographic purification of antibiotics in different matrices". TrAC Trends in Analytical Chemistry. 95: 1–22. doi:10.1016/j.trac.2017.07.023. Retrieved 4 July 2022.
  67. ^ Murphy MB, Fuller ST, Richardson PM, Doyle SA (September 2003). "An improved method for the in vitro evolution of aptamers and applications in protein detection and purification". Nucleic Acids Research. 31 (18): 110e–110. doi:10.1093/nar/gng110. PMC 203336. PMID 12954786.
  68. ^ Chen K, Zhou J, Shao Z, Liu J, Song J, Wang R, et al. (July 2020). "Aptamers as Versatile Molecular Tools for Antibody Production Monitoring and Quality Control". Journal of the American Chemical Society. 142 (28): 12079–12086. doi:10.1021/jacs.9b13370. PMID 32516525. S2CID 219564070.
  69. ^ Keijzer JF, Albada B (March 2022). "DNA-assisted site-selective protein modification". Biopolymers. 113 (3): e23483. doi:10.1002/bip.23483. PMC 9285461. PMID 34878181. S2CID 244954278.
  70. ^ Smith D, Collins BD, Heil J, Koch TH (January 2003). "Sensitivity and specificity of photoaptamer probes". Molecular & Cellular Proteomics. 2 (1): 11–18. doi:10.1074/mcp.m200059-mcp200. PMID 12601078. S2CID 13406870.
  71. ^ Vinkenborg JL, Mayer G, Famulok M (September 2012). "Aptamer-based affinity labeling of proteins". Angewandte Chemie. 51 (36): 9176–9180. doi:10.1002/anie.201204174. PMID 22865679.
  72. ^ Keijzer JF, Firet J, Albada B (December 2021). "Site-selective and inducible acylation of thrombin using aptamer-catalyst conjugates". Chemical Communications. 57 (96): 12960–12963. doi:10.1039/d1cc05446e. PMID 34792071. S2CID 243998479.
  73. ^ Wilson, Brandon D.; Soh, H. Tom (2020-08-01). "Re-Evaluating the Conventional Wisdom about Binding Assays". Trends in Biochemical Sciences. 45 (8): 639–649. doi:10.1016/j.tibs.2020.04.005. ISSN 0968-0004. PMC 7368832. PMID 32402748.
  74. ^ Janson, Jan-Christer (2012-01-03). Protein Purification: Principles, High Resolution Methods, and Applications. John Wiley & Sons. ISBN 978-1-118-00219-3.
  75. ^ Chen A, Yang S (September 2015). "Replacing antibodies with aptamers in lateral flow immunoassay". Biosensors & Bioelectronics. 71: 230–242. doi:10.1016/j.bios.2015.04.041. PMID 25912679.
  76. ^ Toh SY, Citartan M, Gopinath SC, Tang TH (February 2015). "Aptamers as a replacement for antibodies in enzyme-linked immunosorbent assay". Biosensors & Bioelectronics. 64: 392–403. doi:10.1016/j.bios.2014.09.026. PMID 25278480.
  77. ^ Bruno JG, Sivils JC (2016). "Aptamer "Western" blotting for E. coli outer membrane proteins and key virulence factors in pathogenic E. coli serotypes". Aptamers and Synthetic Antibodies.
  78. ^ Bauer M, Macdonald J, Henri J, Duan W, Shigdar S (June 2016). "The Application of Aptamers for Immunohistochemistry". Nucleic Acid Therapeutics. 26 (3): 120–126. doi:10.1089/nat.2015.0569. PMID 26862683.
  79. ^ Meyer M, Scheper T, Walter JG (August 2013). "Aptamers: versatile probes for flow cytometry". Applied Microbiology and Biotechnology. 97 (16): 7097–7109. doi:10.1007/s00253-013-5070-z. PMID 23838792. S2CID 13996688.
  80. ^ Zhou J, Rossi J (March 2017). "Aptamers as targeted therapeutics: current potential and challenges". Nature Reviews. Drug Discovery. 16 (3): 181–202. doi:10.1038/nrd.2016.199. PMC 5700751. PMID 27807347.
  81. ^ Bruno JG (April 2015). "Predicting the Uncertain Future of Aptamer-Based Diagnostics and Therapeutics". Molecules. 20 (4): 6866–6887. doi:10.3390/molecules20046866. PMC 6272696. PMID 25913927.
  82. ^ Wang T, Chen C, Larcher LM, Barrero RA, Veedu RN (2019). "Three decades of nucleic acid aptamer technologies: Lessons learned, progress and opportunities on aptamer development". Biotechnology Advances. 37 (1): 28–50. doi:10.1016/j.biotechadv.2018.11.001. PMID 30408510. S2CID 53242220.
  83. ^ Melbourne J, Bishop P, Brown J, Stoddart G (October 2016). "A multi-faceted approach to achieving the global acceptance of animal-free research methods". Alternatives to Laboratory Animals. 44 (5): 495–498. doi:10.1177/026119291604400511. PMID 27805832. S2CID 1002312.
  84. ^ Alfaleh MA, Alsaab HO, Mahmoud AB, Alkayyal AA, Jones ML, Mahler SM, Hashem AM (2020). "Phage Display Derived Monoclonal Antibodies: From Bench to Bedside". Frontiers in Immunology. 11: 1986. doi:10.3389/fimmu.2020.01986. PMC 7485114. PMID 32983137.
  85. ^ Soontornworajit B, Zhou J, Shaw MT, Fan TH, Wang Y (March 2010). "Hydrogel functionalization with DNA aptamers for sustained PDGF-BB release". Chemical Communications. 46 (11): 1857–1859. doi:10.1039/B924909E. PMID 20198232.
  86. ^ Battig MR, Soontornworajit B, Wang Y (August 2012). "Programmable release of multiple protein drugs from aptamer-functionalized hydrogels via nucleic acid hybridization". Journal of the American Chemical Society. 134 (30): 12410–12413. doi:10.1021/ja305238a. PMID 22816442.
  87. ^ Stejskalová A, Oliva N, England FJ, Almquist BD (February 2019). "Biologically Inspired, Cell-Selective Release of Aptamer-Trapped Growth Factors by Traction Forces". Advanced Materials. 31 (7): e1806380. Bibcode:2019AdM....3106380S. doi:10.1002/adma.201806380. PMC 6375388. PMID 30614086.
  88. ^ Berezovski MV, Lechmann M, Musheev MU, Mak TW, Krylov SN (July 2008). "Aptamer-facilitated biomarker discovery (AptaBiD)". Journal of the American Chemical Society. 130 (28): 9137–9143. doi:10.1021/ja801951p. PMID 18558676.
  89. ^ Colas P, Cohen B, Jessen T, Grishina I, McCoy J, Brent R (April 1996). "Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2". Nature. 380 (6574): 548–550. Bibcode:1996Natur.380..548C. doi:10.1038/380548a0. PMID 8606778. S2CID 4327303.
  90. ^ Nolan GP (January 2005). "Tadpoles by the tail". Nature Methods. 2 (1): 11–12. doi:10.1038/nmeth0105-11. PMID 15782163. S2CID 1423778.
  91. ^ Spolar RS, Record MT (February 1994). "Coupling of local folding to site-specific binding of proteins to DNA". Science. 263 (5148): 777–784. Bibcode:1994Sci...263..777S. doi:10.1126/science.8303294. PMID 8303294.
  92. ^ Huang J, Ru B, Zhu P, Nie F, Yang J, Wang X, et al. (January 2012). "MimoDB 2.0: a mimotope database and beyond". Nucleic Acids Research. 40 (Database issue): D271–D277. doi:10.1093/nar/gkr922. PMC 3245166. PMID 22053087.
  93. ^ "MimoDB: a mimotope database and beyond". immunet.cn. Archived from the original on 2012-11-16. Retrieved 2016-02-03.
  94. ^ Geyer CR, Colman-Lerner A, Brent R (July 1999). ""Mutagenesis" by peptide aptamers identifies genetic network members and pathway connections". Proceedings of the National Academy of Sciences of the United States of America. 96 (15): 8567–8572. Bibcode:1999PNAS...96.8567G. doi:10.1073/pnas.96.15.8567. PMC 17557. PMID 10411916.
  95. ^ Dibenedetto S, Cluet D, Stebe PN, Baumle V, Léault J, Terreux R, et al. (July 2013). "Calcineurin A versus NS5A-TP2/HD domain containing 2: a case study of site-directed low-frequency random mutagenesis for dissecting target specificity of peptide aptamers". Molecular & Cellular Proteomics. 12 (7): 1939–1952. doi:10.1074/mcp.M112.024612. PMC 3708177. PMID 23579184.
  96. ^ Colas P, Cohen B, Ko Ferrigno P, Silver PA, Brent R (December 2000). "Targeted modification and transportation of cellular proteins". Proceedings of the National Academy of Sciences of the United States of America. 97 (25): 13720–13725. Bibcode:2000PNAS...9713720C. doi:10.1073/pnas.97.25.13720. PMC 17642. PMID 11106396.
  97. ^ "FDA Approves Eyetech/Pfizer's Macugen". Review of Ophthalmology. Retrieved 30 June 2022.
  98. ^ Dutt S. "SomaLogic and Illumina Combine Strengths to Propel Innovation in Proteomics". BioSpace. Retrieved 30 June 2022.
  99. ^ "Apta-Index™ (Aptamer Database) - Library of 500+ Aptamers". APTAGEN, LLC. Retrieved 2022-12-16.

Further reading[edit]