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Biomedicines 2018, 6(3), 74; https://doi.org/10.3390/biomedicines6030074

Targeting TGFβ Signaling to Address Fibrosis Using Antisense Oligonucleotides

Centre for Gene and Cell Therapy, School of Biological Sciences, Royal Holloway-University of London, Egham, Surrey TW20 0EX, UK
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Received: 29 May 2018 / Revised: 13 June 2018 / Accepted: 14 June 2018 / Published: 25 June 2018
(This article belongs to the Special Issue Antisense Therapy)
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Abstract

Fibrosis results from the excessive accumulation of extracellular matrix in chronically injured tissue. The fibrotic process is governed by crosstalk between many signaling pathways. The search for an effective treatment is further complicated by the fact that there is a degree of tissue-specificity in the pathways involved, although the process is not completely understood for all tissues. A plethora of drugs have shown promise in pre-clinical models, which is not always borne out translationally in clinical trial. With the recent approvals of two antisense oligonucleotides for the treatment of the genetic diseases Duchenne muscular dystrophy and spinal muscular atrophy, we explore here the potential of antisense oligonucleotides to knockdown the expression of pro-fibrotic proteins. We give an overview of the generalized fibrotic process, concentrating on key players and highlight where antisense oligonucleotides have been used effectively in cellular and animal models of different fibrotic conditions. Consideration is given to the advantages antisense oligonucleotides would have as an anti-fibrotic therapy alongside factors that would need to be addressed to improve efficacy. A prospective outlook for the development of antisense oligonucleotides to target fibrosis is outlined. View Full-Text
Keywords: fibrosis; transforming growth factor beta; antisense oligonucleotide fibrosis; transforming growth factor beta; antisense oligonucleotide
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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March, J.T.; Golshirazi, G.; Cernisova, V.; Carr, H.; Leong, Y.; Lu-Nguyen, N.; Popplewell, L.J. Targeting TGFβ Signaling to Address Fibrosis Using Antisense Oligonucleotides. Biomedicines 2018, 6, 74.

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