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

• Main Authors: Godfrey, Caroline, Desviat, Lourdes R., Arechavala-Gameza, Virginia
• Other Authors: Telethon Italia, Duchenne Parent Project, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Association Française contre les Myopathies, Fundación Ramón Areces, European Commission
• Format: Article in Journal/Newspaper
• Language: unknown
• Published: 2017
• Subjects: Antisense oligonucleotides; Pre-clinical models; Delivery; Toxicity; RNA therapy; Tromsø
• Online Access: http://hdl.handle.net/10261/165480; https://doi.org/10.15252/emmm.201607199; https://doi.org/10.13039/100008054; https://doi.org/10.13039/501100003329; https://doi.org/10.13039/501100004587; https://doi.org/10.13039/100007393; https://doi.org/10.13039/501100000780; https://doi.org/10.13039/501100007423

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. Fundación Ramón Areces and from Spanish Ministry of Economy and Competitiveness and European Regional Development Fund [grant reference SAF2013-43005-R]. B.S. was supported by a grant from the Tromsø Research Foundation. F.P.R. was supported by the Association Française contre les Myopathies (AFM-téléthon). M.A.D. was supported by Telethon Italia [grant reference GGP08244] and Italian Ministry of Health [grant reference GR-2008-1136933 and RF-2011-02347694]. S.L. was supported by The Dutch Duchenne Parent Project NL (DPP NL) and Association Française contre les Myopathies (AFM-téléthon). G.N.G. holds a Miguel Servet Fellowship from the ISCIII (grant reference CP14/00032] and a Fondo de Investigaciones Sanitarias Grant [grant reference PI15/01756], both are partfunded by the European Regional Development Fund (ERDF/FEDER). V.S. was supported by SKIP-NMD project, a European Community’s Seventh Peer Reviewed