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Functionally Enhanced XNA Aptamers Discovered by Parallelized Library Screening
[Image: see text] In vitro evolution strategies have been used for >30 years to generate nucleic acid aptamers against therapeutic targets of interest, including disease-associated proteins. However, this process requires many iterative cycles of selection and amplification, which severely restri...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10690791/ https://www.ncbi.nlm.nih.gov/pubmed/37962593 http://dx.doi.org/10.1021/jacs.3c09497 |
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author | Lozoya-Colinas, Adriana Yu, Yutong Chaput, John C. |
author_facet | Lozoya-Colinas, Adriana Yu, Yutong Chaput, John C. |
author_sort | Lozoya-Colinas, Adriana |
collection | PubMed |
description | [Image: see text] In vitro evolution strategies have been used for >30 years to generate nucleic acid aptamers against therapeutic targets of interest, including disease-associated proteins. However, this process requires many iterative cycles of selection and amplification, which severely restricts the number of target and library design combinations that can be explored in parallel. Here, we describe a single-round screening approach to aptamer discovery that relies on function-enhancing chemotypes to increase the distribution of high-affinity sequences in a random-sequence library. We demonstrate the success of de novo discovery by affinity selection of threomers against the receptor binding domain of the S1 protein from SARS-CoV-2. Detailed biochemical characterization of the enriched population identified threomers with binding affinity values that are comparable to aptamers produced by conventional SELEX. This work establishes a highly parallelizable path for querying diverse chemical repertoires and may offer a viable route for accelerating the discovery of therapeutic aptamers. |
format | Online Article Text |
id | pubmed-10690791 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-106907912023-12-02 Functionally Enhanced XNA Aptamers Discovered by Parallelized Library Screening Lozoya-Colinas, Adriana Yu, Yutong Chaput, John C. J Am Chem Soc [Image: see text] In vitro evolution strategies have been used for >30 years to generate nucleic acid aptamers against therapeutic targets of interest, including disease-associated proteins. However, this process requires many iterative cycles of selection and amplification, which severely restricts the number of target and library design combinations that can be explored in parallel. Here, we describe a single-round screening approach to aptamer discovery that relies on function-enhancing chemotypes to increase the distribution of high-affinity sequences in a random-sequence library. We demonstrate the success of de novo discovery by affinity selection of threomers against the receptor binding domain of the S1 protein from SARS-CoV-2. Detailed biochemical characterization of the enriched population identified threomers with binding affinity values that are comparable to aptamers produced by conventional SELEX. This work establishes a highly parallelizable path for querying diverse chemical repertoires and may offer a viable route for accelerating the discovery of therapeutic aptamers. American Chemical Society 2023-11-14 /pmc/articles/PMC10690791/ /pubmed/37962593 http://dx.doi.org/10.1021/jacs.3c09497 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Lozoya-Colinas, Adriana Yu, Yutong Chaput, John C. Functionally Enhanced XNA Aptamers Discovered by Parallelized Library Screening |
title | Functionally
Enhanced XNA Aptamers Discovered by Parallelized
Library Screening |
title_full | Functionally
Enhanced XNA Aptamers Discovered by Parallelized
Library Screening |
title_fullStr | Functionally
Enhanced XNA Aptamers Discovered by Parallelized
Library Screening |
title_full_unstemmed | Functionally
Enhanced XNA Aptamers Discovered by Parallelized
Library Screening |
title_short | Functionally
Enhanced XNA Aptamers Discovered by Parallelized
Library Screening |
title_sort | functionally
enhanced xna aptamers discovered by parallelized
library screening |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10690791/ https://www.ncbi.nlm.nih.gov/pubmed/37962593 http://dx.doi.org/10.1021/jacs.3c09497 |
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