The Use of Tricyclo-DNA Oligomers for the Treatment of Genetic Disorders
Antisense Oligonucleotides (ASOs) represent very attractive therapeutic compounds for the treatment of numerous diseases. The antisense field has remarkably progressed over the last few years with the approval of the first antisense drugs and with promising developments of more potent and nuclease r...
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doaj-3d4153fb72454f65aaf62705c95d91162020-11-25T00:51:51ZengMDPI AGBiomedicines2227-90592017-12-0161210.3390/biomedicines6010002biomedicines6010002The Use of Tricyclo-DNA Oligomers for the Treatment of Genetic DisordersPhilippine Aupy0Lucía Echevarría1Karima Relizani2Aurélie Goyenvalle3INSERM U1179, UFR des Sciences de la Santé, University of Versailles St-Quentin, 78180 Montigny le Bretonneux, FranceINSERM U1179, UFR des Sciences de la Santé, University of Versailles St-Quentin, 78180 Montigny le Bretonneux, FranceINSERM U1179, UFR des Sciences de la Santé, University of Versailles St-Quentin, 78180 Montigny le Bretonneux, FranceINSERM U1179, UFR des Sciences de la Santé, University of Versailles St-Quentin, 78180 Montigny le Bretonneux, FranceAntisense Oligonucleotides (ASOs) represent very attractive therapeutic compounds for the treatment of numerous diseases. The antisense field has remarkably progressed over the last few years with the approval of the first antisense drugs and with promising developments of more potent and nuclease resistant chemistries. Despite these recent clinical successes and advances in chemistry and design, effective delivery of ASOs to their target tissues remains a major issue. This review will describe the latest advances obtained with the tricyclo-DNA (tcDNA) chemistry which displays unique pharmacological properties and unprecedented uptake in many tissues after systemic administration. We will examine the variety of therapeutic approaches using both fully modified tcDNA-ASOs and gapmers, including splice switching applications, correction of aberrant splicing, steric blocking strategies and targeted gene knock-down mediated by RNase H recruitment. We will then discuss the merits and potential liabilities of the tcDNA chemistry in the context of ASO drug development.https://www.mdpi.com/2227-9059/6/1/2antisense oligonucleotidestricyclo-DNAgapmerssplice-switchingexon-skippingexon-re-inclusiondelivery |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Philippine Aupy Lucía Echevarría Karima Relizani Aurélie Goyenvalle |
spellingShingle |
Philippine Aupy Lucía Echevarría Karima Relizani Aurélie Goyenvalle The Use of Tricyclo-DNA Oligomers for the Treatment of Genetic Disorders Biomedicines antisense oligonucleotides tricyclo-DNA gapmers splice-switching exon-skipping exon-re-inclusion delivery |
author_facet |
Philippine Aupy Lucía Echevarría Karima Relizani Aurélie Goyenvalle |
author_sort |
Philippine Aupy |
title |
The Use of Tricyclo-DNA Oligomers for the Treatment of Genetic Disorders |
title_short |
The Use of Tricyclo-DNA Oligomers for the Treatment of Genetic Disorders |
title_full |
The Use of Tricyclo-DNA Oligomers for the Treatment of Genetic Disorders |
title_fullStr |
The Use of Tricyclo-DNA Oligomers for the Treatment of Genetic Disorders |
title_full_unstemmed |
The Use of Tricyclo-DNA Oligomers for the Treatment of Genetic Disorders |
title_sort |
use of tricyclo-dna oligomers for the treatment of genetic disorders |
publisher |
MDPI AG |
series |
Biomedicines |
issn |
2227-9059 |
publishDate |
2017-12-01 |
description |
Antisense Oligonucleotides (ASOs) represent very attractive therapeutic compounds for the treatment of numerous diseases. The antisense field has remarkably progressed over the last few years with the approval of the first antisense drugs and with promising developments of more potent and nuclease resistant chemistries. Despite these recent clinical successes and advances in chemistry and design, effective delivery of ASOs to their target tissues remains a major issue. This review will describe the latest advances obtained with the tricyclo-DNA (tcDNA) chemistry which displays unique pharmacological properties and unprecedented uptake in many tissues after systemic administration. We will examine the variety of therapeutic approaches using both fully modified tcDNA-ASOs and gapmers, including splice switching applications, correction of aberrant splicing, steric blocking strategies and targeted gene knock-down mediated by RNase H recruitment. We will then discuss the merits and potential liabilities of the tcDNA chemistry in the context of ASO drug development. |
topic |
antisense oligonucleotides tricyclo-DNA gapmers splice-switching exon-skipping exon-re-inclusion delivery |
url |
https://www.mdpi.com/2227-9059/6/1/2 |
work_keys_str_mv |
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