Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1785111179635458048 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10527716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT manglapriyanka therapeuticoligonucleotidesanoutlookonchemicalstrategiestoimproveendosomaltrafficking AT vicentiniquentin therapeuticoligonucleotidesanoutlookonchemicalstrategiestoimproveendosomaltrafficking AT biscansannabelle therapeuticoligonucleotidesanoutlookonchemicalstrategiestoimproveendosomaltrafficking |