Delivery is key: lessons learnt from developing splice-switching antisense therapies
Godfrey, Caroline (University of Oxford. Department of Physiology, Anatomy and Genetics)
Desviat, Lourdes R. (Centro de Biología Molecular Severo Ochoa)
Smedsrød, Bård (University of TromsØ. Department of Medical Biology)
Piétri-Rouxel, France (Institut de Myologie (París, França))
Denti, Michela A. (Università di Trento. Centre for Integrative Biology)
Disterer, Petra (University College London. Centre for Amyloidosis and Acute Phase Proteins)
Lorain, Stéphanie (Institut de Myologie (París, França))
Nogales, Gisela (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Sardone, Valentina (University College London)
Anwar, Rayan (Drug Discovery Informatics Lap, Qasemi-Research Center, Al-Qasemi Academic College)
E. L. Andaloussi, Samir (Karolinska Institutet (Estocolm, Suècia). Department of Laboratory Medicine)
Lehto, Taavi (University of Tartu. Institute of Technology)
Khoo, Bernard (University College London. Centre for Neuroendocrinology)
Brolin, Camilla (University of Copenhagen. Department of Cellular and Molecular Medicine)
van Roon-Mom, Willeke M. C. (Leiden University Medical Center. DEpartment of Human Genetics)
Goyenvalle, Aurélie (Université Versailles Saint Quentin)
Aartsma-Rus, Annemieke (Leiden University Medical Center. Department of Human Genetics)
Arechavala-Gomeza, Virginia (Instituto de Investigación Sanitaria Biocruces Bizkaia)
Universitat Autònoma de Barcelona

Date:	2017
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article de revisió ; Article ; Versió publicada
Subject:	Antisense oligonucleotides ; Delivery ; Pre-clinical models ; RNA therapy ; Toxicity
Published in:	EMBO Molecular Medicine, Vol. 9 Núm. 5 (2017) , p. 545-557, ISSN 1757-4684

DOI: 10.15252/emmm.201607199
PMID: 28289078

13 p, 1.6 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Published articles