Delivery is key: lessons learnt from developing splice‐switching antisense therapies

Abstract The use of splice‐switching antisense therapy is highly promising, with a wealth of pre‐clinical data and numerous clinical trials ongoing. Nevertheless, its potential to treat a variety of disorders has yet to be realized. The main obstacle impeding the clinical translation of this approac...

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Main Authors: Caroline Godfrey, Lourdes R Desviat, Bård Smedsrød, France Piétri‐Rouxel, Michela A Denti, Petra Disterer, Stéphanie Lorain, Gisela Nogales‐Gadea, Valentina Sardone, Rayan Anwar, Samir EL Andaloussi, Taavi Lehto, Bernard Khoo, Camilla Brolin, Willeke MC van Roon‐Mom, Aurélie Goyenvalle, Annemieke Aartsma‐Rus, Virginia Arechavala‐Gomeza
Format: Article
Language:English
Published: Springer Nature 2017-03-01
Series:EMBO Molecular Medicine
Subjects:
Online Access:https://doi.org/10.15252/emmm.201607199
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author Caroline Godfrey
Lourdes R Desviat
Bård Smedsrød
France Piétri‐Rouxel
Michela A Denti
Petra Disterer
Stéphanie Lorain
Gisela Nogales‐Gadea
Valentina Sardone
Rayan Anwar
Samir EL Andaloussi
Taavi Lehto
Bernard Khoo
Camilla Brolin
Willeke MC van Roon‐Mom
Aurélie Goyenvalle
Annemieke Aartsma‐Rus
Virginia Arechavala‐Gomeza
author_facet Caroline Godfrey
Lourdes R Desviat
Bård Smedsrød
France Piétri‐Rouxel
Michela A Denti
Petra Disterer
Stéphanie Lorain
Gisela Nogales‐Gadea
Valentina Sardone
Rayan Anwar
Samir EL Andaloussi
Taavi Lehto
Bernard Khoo
Camilla Brolin
Willeke MC van Roon‐Mom
Aurélie Goyenvalle
Annemieke Aartsma‐Rus
Virginia Arechavala‐Gomeza
author_sort Caroline Godfrey
collection DOAJ
description Abstract The use of splice‐switching antisense therapy is highly promising, with a wealth of pre‐clinical data and numerous clinical trials ongoing. Nevertheless, its potential to treat a variety of disorders has yet to be realized. The main obstacle impeding the clinical translation of this approach is the relatively poor delivery of antisense oligonucleotides to target tissues after systemic delivery. We are a group of researchers closely involved in the development of these therapies and would like to communicate our discussions concerning the validity of standard methodologies currently used in their pre‐clinical development, the gaps in current knowledge and the pertinent challenges facing the field. We therefore make recommendations in order to focus future research efforts and facilitate a wider application of therapeutic antisense oligonucleotides.
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spelling doaj-art-dc24c7db81c9430cadef6dc5077b79152025-08-20T03:06:00ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842017-03-019554555710.15252/emmm.201607199Delivery is key: lessons learnt from developing splice‐switching antisense therapiesCaroline Godfrey0Lourdes R Desviat1Bård Smedsrød2France Piétri‐Rouxel3Michela A Denti4Petra Disterer5Stéphanie Lorain6Gisela Nogales‐Gadea7Valentina Sardone8Rayan Anwar9Samir EL Andaloussi10Taavi Lehto11Bernard Khoo12Camilla Brolin13Willeke MC van Roon‐Mom14Aurélie Goyenvalle15Annemieke Aartsma‐Rus16Virginia Arechavala‐Gomeza17Department of Physiology, Anatomy and Genetics, University of OxfordCentro de Biología Molecular Severo Ochoa UAM‐CSIC, CIBERER, IdiPaz, Universidad Autónoma de MadridDepartment of Medical Biology, University of TromsøUPMC, INSERM, UMRS 974, CNRS FRE 3617, Institut de MyologieCentre for Integrative Biology, University of TrentoCentre for Amyloidosis and Acute Phase Proteins, Division of Medicine, University College LondonUPMC, INSERM, UMRS 974, CNRS FRE 3617, Institut de MyologieGrup d'Investigació en Malalties Neuromusculars i Neuropediatriques, Institut d' Investigació en Ciències de la Salut Germans Trias i Pujol, BadalonaDubowitz Neuromuscular Centre and Developmental Neuroscience Programme, Institute of Child Health, University College LondonDrug Discovery Informatics Lab, Qasemi‐Research Center, Al‐Qasemi Academic CollegeDepartment of Physiology, Anatomy and Genetics, University of OxfordDepartment of Laboratory Medicine, Karolinska InstituteCentre for Neuroendocrinology, Division of Medicine, University College LondonDepartment of Cellular and Molecular Medicine, University of CopenhagenDepartment of Human Genetics, Leiden University Medical CenterINSERM U1179, UFR des sciences de la santé, Université Versailles Saint QuentinDepartment of Human Genetics, Leiden University Medical CenterNeuromuscular Disorders Group, BioCruces Health Research Institute, BarakaldoAbstract The use of splice‐switching antisense therapy is highly promising, with a wealth of pre‐clinical data and numerous clinical trials ongoing. Nevertheless, its potential to treat a variety of disorders has yet to be realized. The main obstacle impeding the clinical translation of this approach is the relatively poor delivery of antisense oligonucleotides to target tissues after systemic delivery. We are a group of researchers closely involved in the development of these therapies and would like to communicate our discussions concerning the validity of standard methodologies currently used in their pre‐clinical development, the gaps in current knowledge and the pertinent challenges facing the field. We therefore make recommendations in order to focus future research efforts and facilitate a wider application of therapeutic antisense oligonucleotides.https://doi.org/10.15252/emmm.201607199antisense oligonucleotidesdeliverypre‐clinical modelsRNA therapytoxicity
spellingShingle Caroline Godfrey
Lourdes R Desviat
Bård Smedsrød
France Piétri‐Rouxel
Michela A Denti
Petra Disterer
Stéphanie Lorain
Gisela Nogales‐Gadea
Valentina Sardone
Rayan Anwar
Samir EL Andaloussi
Taavi Lehto
Bernard Khoo
Camilla Brolin
Willeke MC van Roon‐Mom
Aurélie Goyenvalle
Annemieke Aartsma‐Rus
Virginia Arechavala‐Gomeza
Delivery is key: lessons learnt from developing splice‐switching antisense therapies
EMBO Molecular Medicine
antisense oligonucleotides
delivery
pre‐clinical models
RNA therapy
toxicity
title Delivery is key: lessons learnt from developing splice‐switching antisense therapies
title_full Delivery is key: lessons learnt from developing splice‐switching antisense therapies
title_fullStr Delivery is key: lessons learnt from developing splice‐switching antisense therapies
title_full_unstemmed Delivery is key: lessons learnt from developing splice‐switching antisense therapies
title_short Delivery is key: lessons learnt from developing splice‐switching antisense therapies
title_sort delivery is key lessons learnt from developing splice switching antisense therapies
topic antisense oligonucleotides
delivery
pre‐clinical models
RNA therapy
toxicity
url https://doi.org/10.15252/emmm.201607199
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