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Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking

The potential of oligonucleotide therapeutics is undeniable as more than 15 drugs have been approved to treat various diseases in the liver, central nervous system (CNS), and muscles. However, achieving effective delivery of oligonucleotide therapeutics to specific tissues still remains a major chal...

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Detalles Bibliográficos
Autores principales: Mangla, Priyanka, Vicentini, Quentin, Biscans, Annabelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527716/
https://www.ncbi.nlm.nih.gov/pubmed/37759475
http://dx.doi.org/10.3390/cells12182253
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author Mangla, Priyanka
Vicentini, Quentin
Biscans, Annabelle
author_facet Mangla, Priyanka
Vicentini, Quentin
Biscans, Annabelle
author_sort Mangla, Priyanka
collection PubMed
description The potential of oligonucleotide therapeutics is undeniable as more than 15 drugs have been approved to treat various diseases in the liver, central nervous system (CNS), and muscles. However, achieving effective delivery of oligonucleotide therapeutics to specific tissues still remains a major challenge, limiting their widespread use. Chemical modifications play a crucial role to overcome biological barriers to enable efficient oligonucleotide delivery to the tissues/cells of interest. They provide oligonucleotide metabolic stability and confer favourable pharmacokinetic/pharmacodynamic properties. This review focuses on the various chemical approaches implicated in mitigating the delivery problem of oligonucleotides and their limitations. It highlights the importance of linkers in designing oligonucleotide conjugates and discusses their potential role in escaping the endosomal barrier, a bottleneck in the development of oligonucleotide therapeutics.
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spelling pubmed-105277162023-09-28 Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking Mangla, Priyanka Vicentini, Quentin Biscans, Annabelle Cells Review The potential of oligonucleotide therapeutics is undeniable as more than 15 drugs have been approved to treat various diseases in the liver, central nervous system (CNS), and muscles. However, achieving effective delivery of oligonucleotide therapeutics to specific tissues still remains a major challenge, limiting their widespread use. Chemical modifications play a crucial role to overcome biological barriers to enable efficient oligonucleotide delivery to the tissues/cells of interest. They provide oligonucleotide metabolic stability and confer favourable pharmacokinetic/pharmacodynamic properties. This review focuses on the various chemical approaches implicated in mitigating the delivery problem of oligonucleotides and their limitations. It highlights the importance of linkers in designing oligonucleotide conjugates and discusses their potential role in escaping the endosomal barrier, a bottleneck in the development of oligonucleotide therapeutics. MDPI 2023-09-11 /pmc/articles/PMC10527716/ /pubmed/37759475 http://dx.doi.org/10.3390/cells12182253 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mangla, Priyanka
Vicentini, Quentin
Biscans, Annabelle
Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking
title Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking
title_full Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking
title_fullStr Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking
title_full_unstemmed Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking
title_short Therapeutic Oligonucleotides: An Outlook on Chemical Strategies to Improve Endosomal Trafficking
title_sort therapeutic oligonucleotides: an outlook on chemical strategies to improve endosomal trafficking
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527716/
https://www.ncbi.nlm.nih.gov/pubmed/37759475
http://dx.doi.org/10.3390/cells12182253
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