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Aptamers (from the Latin ''aptus'' - fit, and Greek ''meros'' - part) are oligonucleotide or peptide molecules that bind to a specific target molecule. Aptamers are usually created by selecting them from a large random sequence pool, but natural aptamers also exist in riboswitches. Aptamers can be used for both basic research and clinical purposes as macromolecular drugs. Aptamers can be combined with ribozymes to self-cleave in the presence of their target molecule. These compound molecules have additional research, industrial and clinical applications. More specifically, aptamers can be classified as: * DNA or RNA or XNA aptamers. They consist of (usually short) strands of oligonucleotides. * Peptide aptamers. They consist of a short variable peptide domain, attached at both ends to a protein scaffold. ==Nucleic Acid aptamers== Nucleic acid aptamers are nucleic acid species that have been engineered through repeated rounds of ''in vitro selection'' or equivalently, SELEX (systematic evolution of ligands by exponential enrichment) to bind to various molecular targets such as small molecules, proteins, nucleic acids, and even cells, tissues and organisms. Aptamers are useful in biotechnological and therapeutic applications as they offer molecular recognition properties that rival that of the commonly used biomolecule, antibodies. In addition to their discriminate recognition, aptamers offer advantages over antibodies as they can be engineered completely in a test tube, are readily produced by chemical synthesis, possess desirable storage properties, and elicit little or no immunogenicity in therapeutic applications. In 1990, two labs independently developed the technique of selection: the Gold lab, using the term SELEX for their process of selecting RNA ligands against T4 DNA polymerase; and the Szostak lab, coining the term ''in vitro selection'', selecting RNA ligands against various organic dyes. The Szostak lab also coined the term aptamer (from the Latin, ''apto'', meaning ‘to fit’) for these nucleic acid-based ligands. Two years later, the Szostak lab and Gilead Sciences, independent of one another, used ''in vitro selection'' schemes to evolve single stranded DNA ligands for organic dyes and human coagulant, thrombin (see Anti-thrombin aptamers), respectively. There does not appear to be any systematic differences between RNA and DNA aptamers, save the greater intrinsic chemical stability of DNA. Interestingly enough, the notion of selection ''in vitro'' was actually preceded twenty-plus years prior when Sol Spiegelman used a Qbeta replication system as a way to evolve a self-replicating molecule. In addition, a year before the publishing of ''in vitro selection'' and SELEX, Gerald Joyce used a system that he termed ‘directed evolution’ to alter the cleavage activity of a ribozyme. Since the discovery of aptamers, many researchers have used aptamer selection as a means for application and discovery. In 2001, the process of ''in vitro selection'' was automated by J. Colin Cox in the Ellington lab at the University of Texas at Austin, reducing the duration of a selection experiment from six weeks to three days. While the process of artificial engineering of nucleic acid ligands is highly interesting to biology and biotechnology, the notion of aptamers in the natural world had yet to be uncovered until 2002 when two groups led by Ronald Breaker and Evgeny Nudler discovered a nucleic acid-based genetic regulatory element (which was named riboswitch) that possesses similar molecular recognition properties to the artificially made aptamers. In addition to the discovery of a new mode of genetic regulation, this adds further credence to the notion of an ‘RNA World,’ a postulated stage in time in the origins of life on Earth. Both DNA and RNA aptamers show robust binding affinities for various targets. DNA and RNA aptamers have been selected for the same target. These targets include lysozyme, thrombin, human immunodeficiency virus trans-acting responsive element (HIV TAR), hemin, interferon γ, vascular endothelial growth factor (VEGF), prostate specific antigen (PSA), dopamine, and the non-classical oncogene, heat shock factor 1 (HSF1). In the case of lysozyme, HIV TAR, VEGF and dopamine the DNA aptamer is the analog of the RNA aptamer, with thymine replacing uracil. The hemin, thrombin, and interferon γ, DNA and RNA aptamers were selected through independent selections and have unique sequences. Considering that not all DNA analogs of RNA aptamers show functionality the correlation between DNA and RNA sequence and their structure and function requires further investigation. Lately, a concept of smart aptamers, and smart ligands in general, has been introduced. It describes aptamers that are selected with pre-defined equilibrium (), rate (, ) constants and thermodynamic (ΔH, ΔS) parameters of aptamer-target interaction. Kinetic capillary electrophoresis is the technology used for the selection of smart aptamers. It obtains aptamers in a few rounds of selection. Recent developments in aptamer-based therapeutics have been rewarded in the form of the first aptamer-based drug approved by the U.S. Food and Drug Administration (FDA) in treatment for age-related macular degeneration (AMD), called Macugen offered by OSI Pharmaceuticals. In addition, the company NeoVentures Biotechnology Inc. (http://www.neoventures.ca) has successfully commercialized the first aptamer based diagnostic platform for analysis of mycotoxins in grain. Many contract companies develop aptamers and aptabodies to replace antibodies in research, diagnostic platforms, drug discovery, and therapeutics. Non-modified aptamers are cleared rapidly from the bloodstream, with a half-life of minutes to hours, mainly due to nuclease degradation and clearance from the body by the kidneys, a result of the aptamer's inherently low molecular weight. Unmodified aptamer applications currently focus on treating transient conditions such as blood clotting, or treating organs such as the eye where local delivery is possible. This rapid clearance can be an advantage in applications such as ''in vivo'' diagnostic imaging. An example is a tenascin-binding aptamer under development by Schering AG for cancer imaging. Several modifications, such as 2'-fluorine-substituted pyrimidines, polyethylene glycol (PEG) linkage, etc. (both of which are used in Macugen, an FDA-approved aptamer) are available to scientists with which to increase the serum half-life of aptamers easily to the day or even week time scale. Another approach to increase the nuclease resistance of aptamers is to develop Spiegelmers, which are composed entirely of an unnatural L-ribonucleic acid backbone. A spiegelmer of the same sequence has the same binding properties of the corresponding RNA aptamer, except it binds to the mirror image of its target molecule. In addition to the development of aptamer-based therapeutics, many researchers such as the Ellington lab have been developing diagnostic techniques for aptamer based plasma protein profiling called aptamer plasma proteomics. This technology will enable future multi-biomarker protein measurements that can aid diagnostic distinction of disease versus healthy states. Furthermore, the Hirao lab applied a genetic alphabet expansion using an unnatural base pair to SELEX and achieved the generation of high affinity DNA aptamers. Only few hydrophobic unnatural base as a fifth base significantly augment the aptamer affinity to target proteins. As a resource for all ''in vitro selection'' and SELEX experiments, the Ellington lab has developed the Aptamer Database cataloging all published experiments. This is found at http://aptamer.icmb.utexas.edu/. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Aptamer」の詳細全文を読む スポンサード リンク
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