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Aptamers also provide numerous advantages over antibodies. As mentioned, aptamers are oligonucleotides whereas antibodies are proteins. As such, aptamers have a remarkable stability in a wide range of pH and temperatures, have higher shelf lifes, are non-toxic and lack immunogenicity [2, 3]. Other advantages stem from the fact that aptamers are generated in vitro, whereas antibodies are generated through in vivo enrichment followed by purification through monoclonal cell lines [4]. As a result, generation of aptamers is less laborious, production costs are lower and reproducibility is higher. Finally, in contrast to antibodies, aptamers can be generated against virtually any molecule, including toxins and poor immunogenic targets [5]. This places aptamers amongst the most powerful tools in biotechnology [6]. | Aptamers also provide numerous advantages over antibodies. As mentioned, aptamers are oligonucleotides whereas antibodies are proteins. As such, aptamers have a remarkable stability in a wide range of pH and temperatures, have higher shelf lifes, are non-toxic and lack immunogenicity [2, 3]. Other advantages stem from the fact that aptamers are generated in vitro, whereas antibodies are generated through in vivo enrichment followed by purification through monoclonal cell lines [4]. As a result, generation of aptamers is less laborious, production costs are lower and reproducibility is higher. Finally, in contrast to antibodies, aptamers can be generated against virtually any molecule, including toxins and poor immunogenic targets [5]. This places aptamers amongst the most powerful tools in biotechnology [6]. | ||
A major limitation of aptamers in comparison with antibodies is their stability in vivo, where nucleic acids are rapidly degraded. Aptamers which have been used as therapeutic agents, for example, suffered from a half-life of 2 minutes [7]. This problem has, however, partially been overcome by using chemical modifications to the aptamers. An example of these modifications are Spiegelmers [6]. These oligonucleotides’ backbones contain L-Ribose instead of R-Ribose – “spiegel” means mirror. These mirrored aptamers are more stable in vivo, because they suffer less from degradation. | A major limitation of aptamers in comparison with antibodies is their stability in vivo, where nucleic acids are rapidly degraded. Aptamers which have been used as therapeutic agents, for example, suffered from a half-life of 2 minutes [7]. This problem has, however, partially been overcome by using chemical modifications to the aptamers. An example of these modifications are Spiegelmers [6]. These oligonucleotides’ backbones contain L-Ribose instead of R-Ribose – “spiegel” means mirror. These mirrored aptamers are more stable in vivo, because they suffer less from degradation. | ||
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| + | Since aptamers can be easily modified chemically, they can be attached to numerous surfaces, enabling their way into a wide array of biosensors and drug delivery systems. Generally, the biosensors couple binding of the aptamer to a change in structure in the latter, which generates either a fluorescent or electrical signal. Aptamers have also found their way into drug delivery systems. A particular example of such a system is developed by Wu et al., featuring aptamers targeted at cancer cells with lipid tails. These aptamers could be used as building blocks of micelles, enabling efficient delivery of the micelles to cancerous cells [8]. | ||
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Revision as of 12:22, 22 July 2015
The Recognition Element – Aptamers
Since the discovery of the nucleic acid structure, nucleic acids were long thought to have a single function – storage of the heredity information as genetic instructions. Our perception on the function of DNA and RNA changed radically, however, as it was discovered that small RNA molecules could fold into a three-dimensional structure, exposing a surface onto which other small molecules could perfectly fit. Soon after the discovery that nucleic acids could have interaction with other molecules, Craig Tuerk and Larry Gold described a procedure, called SELEX, to isolate high-affinity nucleic acid ligands for proteins through a Darwinian-like evolution process carried out in vitro [1]. This procedure enabled researchers to discover oligonucleotides with high affinities and a perfect fit for arbitrary proteins, cells, small molecules and even viruses. After this perfect fit, these synthetic oligonucleotides were called ‘aptamers’ – stemming from the Latin aptus which can be translated into ‘fit’.
The Rise of Aptamers
25 Years after the discovery of Tuerk’s and Gold’s invention of Systemic Evolution of Ligands by Exponential enrichment (SELEX), aptamers have become available for hundreds of ligands, including proteins, viruses, other small molecules and even whole cells. As such, aptamers have become a viable alternative for biology’s traditional recognition elements, antibodies. Aptamers also provide numerous advantages over antibodies. As mentioned, aptamers are oligonucleotides whereas antibodies are proteins. As such, aptamers have a remarkable stability in a wide range of pH and temperatures, have higher shelf lifes, are non-toxic and lack immunogenicity [2, 3]. Other advantages stem from the fact that aptamers are generated in vitro, whereas antibodies are generated through in vivo enrichment followed by purification through monoclonal cell lines [4]. As a result, generation of aptamers is less laborious, production costs are lower and reproducibility is higher. Finally, in contrast to antibodies, aptamers can be generated against virtually any molecule, including toxins and poor immunogenic targets [5]. This places aptamers amongst the most powerful tools in biotechnology [6]. A major limitation of aptamers in comparison with antibodies is their stability in vivo, where nucleic acids are rapidly degraded. Aptamers which have been used as therapeutic agents, for example, suffered from a half-life of 2 minutes [7]. This problem has, however, partially been overcome by using chemical modifications to the aptamers. An example of these modifications are Spiegelmers [6]. These oligonucleotides’ backbones contain L-Ribose instead of R-Ribose – “spiegel” means mirror. These mirrored aptamers are more stable in vivo, because they suffer less from degradation.
Aptamers in Biotechnology
Since aptamers can be easily modified chemically, they can be attached to numerous surfaces, enabling their way into a wide array of biosensors and drug delivery systems. Generally, the biosensors couple binding of the aptamer to a change in structure in the latter, which generates either a fluorescent or electrical signal. Aptamers have also found their way into drug delivery systems. A particular example of such a system is developed by Wu et al., featuring aptamers targeted at cancer cells with lipid tails. These aptamers could be used as building blocks of micelles, enabling efficient delivery of the micelles to cancerous cells [8].