Delivery is key: lessons learnt from developing splice-switching antisense therapies
AuthorGodfrey, Caroline; Desviat, Lourdes R.; Smedsrød, Bård; Piétri-Rouxel, France; Denti, Michela A.; Disterer, Petra; Lorain, Stéphanie; Nogales-Gadea, Gisela; Sardone, Valentina; Anwar, Rayan; El Andaloussi, Samir; Letho, Taavi; Khoo, Bernard; Brolin, Camilla; Mc Van Roon-Mom, Willeke; Goyenvalle, Aurélie; Aartsma-Rus, Annemieke; Arechavala-Gomeza, Virginia
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 anti- sense 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.
Source at http://doi.org/10.15252/emmm.201607199