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RNA aptamers: from basic science towards therapy.

H Ulrich1

  • 1Department of Biochemistry, Instituto de Química, Universidade de São Paulo, Caixa Postal 26077, São Paulo 05513-970, Brazil. henning@iq.usp.br

Handbook of Experimental Pharmacology
|April 6, 2006
PubMed
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Systematic evolution of ligands by exponential enrichment (SELEX) generates aptamers, which are nucleic acid ligands binding targets like antibodies. Modified aptamers and Spiegelmers offer enhanced stability and therapeutic potential for various diseases.

Area of Science:

  • Biotechnology and Molecular Biology
  • Nucleic Acid Aptamer Technology

Background:

  • Systematic evolution of ligands by exponential enrichment (SELEX) is a key in vitro selection method for discovering nucleic acid ligands (aptamers).
  • Initially used for RNA aptamers binding proteins and small molecules, SELEX has expanded to target diverse molecules, including growth factors and cell surface antigens.
  • Aptamers exhibit antibody-like affinity and specificity, with applications in therapy and diagnostics.

Purpose of the Study:

  • To review the advancements and applications of SELEX technology in generating aptamers for various targets.
  • To highlight the development of aptazymes, intramers, and Spiegelmers for enhanced functionality and therapeutic potential.
  • To discuss the role of chemical modifications in improving aptamer stability and in vivo utility.

Main Methods:

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  • In vitro selection using SELEX to identify nucleic acid aptamers against specific molecular targets.
  • Engineering of aptazymes for combined molecular recognition and catalytic activity.
  • Development of Spiegelmers through selection against D-peptide targets and synthesis of L-RNA aptamers.
  • Chemical modifications of aptamers, such as 2'-OH substitutions, to enhance nuclease resistance.

Main Results:

  • SELEX has successfully identified aptamers with high affinity and specificity for a wide range of targets, including complex ones like cell surface receptors.
  • Modified aptamers and Spiegelmers demonstrate increased resistance to enzymatic degradation, improving their suitability for in vivo applications.
  • Nuclease-resistant aptamers have been developed against disease-associated targets, showing promise in preclinical and clinical studies.

Conclusions:

  • SELEX is a versatile and powerful technology for aptamer discovery with broad therapeutic and diagnostic potential.
  • Chemical modifications and novel aptamer designs like Spiegelmers significantly enhance aptamer stability and efficacy.
  • RNA aptamers, including intramers, are valuable tools for dissecting biological pathways and hold promise for future medical interventions.