Abstract

Aptamers are short, single-stranded nucleic acid sequences that are selected in vitro from large oligonucleotide libraries based on their high affinity to a target molecule. Hence, aptamers can be thought of as a nucleic acid analog to antibodies. However, several viewpoints hold that the potential of aptamers arises from interesting characteristics that are distinct from, or in some cases, superior to those of antibodies. This review summarizes the recent achievements in aptamer programs developed in our laboratory against basic and therapeutic protein targets. Through these studies, we became aware of the remarkable conformational plasticity and selectivity of RNA, on which the published report has not shed much light even though this is evidently a crucial feature for the strong specificity and affinity of RNA aptamers.

Highlights

  • The concept of using single-stranded nucleic acids as affinity molecules for protein or compound binding was initially described in 1990 (Ellington & Szostak 1990, 1992; Tuerk & Gold 1990)

  • This idea arose in our previous studies of the structure– function relationship of translation factors, in which we discovered that translation factors mimic the shape of tRNA

  • PEG212idT injection at day 8 significantly suppressed the progression of arthritis even after it had developed (Ishiguro et al 2011). These results suggest that IL-17A blockade by PEG21-2idT has both protective and therapeutic activity against glucose-6-phosphate isomerase (GPI)-induced arthritis

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Summary

Introduction

The concept of using single-stranded nucleic acids (aptamers) as affinity molecules for protein or compound binding was initially described in 1990 (Ellington & Szostak 1990, 1992; Tuerk & Gold 1990). Nature must have evolved the ‘art’ of molecular mimicry between RNA and proteins using different protein architectures that are functionally active in a ribosome ‘machine’ (Nakamura & Ito 2003) This view reinforces the high potential of RNA for plasticity. The crystal structure of an RNA aptamer in a complex with thrombin, which is not a nucleic acid–binding protein, indicates that the aptamer binds to the positively charged surface of the protein that is naturally required for high-affinity heparin binding (Long et al 2008). The aptamer required divalent cations for binding because the bound IgG was released with the addition of EDTA (Miyakawa et al 2008) To investigate these remarkable properties, we solved the crystal structure of the aptamer–hFc1 complex at the resolution of 2.15 A (Fig. 2A; Nomura et al 2010). It is likely that SELEX technology can select for molecules that interact through predominantly electrostatic forces (Hermann & Patel 2000; Huang et al 2003; Horn et al 2004), and for high-specificity

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Conclusions and perspectives
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