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

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 M.C. van Roon-Mom; Aurélie Goyenvalle; Annemieke Aartsma-Rus; Virginia Arechavala-Gomeza

doi:10.15252/emmm.201607199

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

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 M.C. van Roon-Mom, Aurélie Goyenvalle, Annemieke Aartsma-Rus, Virginia Arechavala-Gomeza^*

^*Corresponding author af dette arbejde

Transcription, RNA, and Gene Medicine Program

61 Citationer (Scopus)

88 Downloads (Pure)

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.

Originalsprog	Engelsk
Tidsskrift	EMBO Molecular Medicine
Vol/bind	9
Udgave nummer	5
Sider (fra-til)	545-557
Antal sider	13
ISSN	1757-4676
DOI	https://doi.org/10.15252/emmm.201607199
Status	Udgivet - maj 2017

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10.15252/emmm.201607199Licens: CC BY

Delivery is key: lessons learnt from developing splice‐switching antisense therapiesForlagets udgivne version, 1,67 MBLicens: CC BY

Citationsformater

Godfrey, C., Desviat, L. R., Smedsrød, B., Piétri-Rouxel, F., Denti, M. A., Disterer, P., Lorain, S., Nogales-Gadea, G., Sardone, V., Anwar, R., El Andaloussi, S., Lehto, T., Khoo, B., Brolin, C., van Roon-Mom, W. M. C., Goyenvalle, A., Aartsma-Rus, A., & Arechavala-Gomeza, V. (2017). Delivery is key: lessons learnt from developing splice-switching antisense therapies. EMBO Molecular Medicine, 9(5), 545-557. https://doi.org/10.15252/emmm.201607199

Godfrey, C, Desviat, LR, Smedsrød, B, Piétri-Rouxel, F, Denti, MA, Disterer, P, Lorain, S, Nogales-Gadea, G, Sardone, V, Anwar, R, El Andaloussi, S, Lehto, T, Khoo, B, Brolin, C, van Roon-Mom, WMC, Goyenvalle, A, Aartsma-Rus, A & Arechavala-Gomeza, V 2017, 'Delivery is key: lessons learnt from developing splice-switching antisense therapies', EMBO Molecular Medicine, bind 9, nr. 5, s. 545-557. https://doi.org/10.15252/emmm.201607199

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title = "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 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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author = "Caroline Godfrey and Desviat, {Lourdes R.} and B{\aa}rd Smedsr{\o}d and France Pi{\'e}tri-Rouxel and Denti, {Michela A.} and Petra Disterer and St{\'e}phanie Lorain and Gisela Nogales-Gadea and Valentina Sardone and Rayan Anwar and {El Andaloussi}, Samir and Taavi Lehto and Bernard Khoo and Camilla Brolin and {van Roon-Mom}, {Willeke M.C.} and Aur{\'e}lie Goyenvalle and Annemieke Aartsma-Rus and Virginia Arechavala-Gomeza",

year = "2017",

month = may,

doi = "10.15252/emmm.201607199",

language = "English",

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AU - Godfrey, Caroline

AU - Desviat, Lourdes R.

AU - Smedsrød, Bård

AU - Piétri-Rouxel, France

AU - Denti, Michela A.

AU - Disterer, Petra

AU - Lorain, Stéphanie

AU - Nogales-Gadea, Gisela

AU - Sardone, Valentina

AU - Anwar, Rayan

AU - El Andaloussi, Samir

AU - Lehto, Taavi

AU - Khoo, Bernard

AU - Brolin, Camilla

AU - van Roon-Mom, Willeke M.C.

AU - Goyenvalle, Aurélie

AU - Aartsma-Rus, Annemieke

AU - Arechavala-Gomeza, Virginia

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N2 - 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.

AB - 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.

KW - antisense oligonucleotides

KW - delivery

KW - pre-clinical models

KW - RNA therapy

KW - toxicity

U2 - 10.15252/emmm.201607199

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M3 - Review

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EP - 557

JO - EMBO Molecular Medicine

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ER -

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

Abstract

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