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Improving aptamer performance with nucleic acid mimics: de novo and post-SELEX approaches

Journal

TRENDS IN BIOTECHNOLOGY
Volume 40, Issue 5, Pages 549-563

Publisher

CELL PRESS
DOI: 10.1016/j.tibtech.2021.09.011

Keywords

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Funding

  1. Project NAM4toxins [POCI-01-0145-FEDER-028659]
  2. FEDER funds through COMPETE2020 -Programa Operacional Competitividade e Internacionalizacao (POCI)
  3. national funds (PIDDAC) through FCT (Fundacao para a Ciencia e a Tecnologia)
  4. Laboratory for Process Engineering, Environment, Biotechnology and Energy -LEPABE - national funds through the FCT (PIDDAC) [UIDB/00511/2020]
  5. unit and BioTecNorte operation - FCT under the scope of the European Regional Development Fund (Norte2020 -Programa Operacional Regional do Norte) [UIDB/04469/2020, NORTE-01-0145-FEDER-000004]
  6. FCT [SFRH/BD/138883/2018]
  7. Fundação para a Ciência e a Tecnologia [SFRH/BD/138883/2018] Funding Source: FCT

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This article discusses the advantages and limitations of using nucleic acid mimics to enhance the versatility of aptamers, including the applicability of existing engineered polymerases to replicate nucleic acid mimics and methodologies to improve aptamers. It also explores the limitations of existing methods for sequencing nucleic acid mimic sequences and bioinformatic tools for predicting aptamer structures.
Aptamers are structural single-stranded oligonucleotides generated in vitro to bind to a specific target molecule. Aptamers' versatility can be enhanced with nucleic acid mimics (NAMs) during or after a selection process, also known as systematic evolution of ligands by exponential enrichment (SELEX). We address advantages and limitations of the technologies used to generate NAM aptamers, especially the applicability of existing engineered polymerases to replicate NAMs and methodologies to improve aptamers after SELEX. We also discuss the limitations of existing methods for sequencing NAM sequences and bioinformatic tools to predict NAM aptamer structures. As a conclusion, we suggest that NAM aptamers might successfully compete with molecular tools based on proteins such as antibodies for future application.

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