Therapeutic Oligonucleotides Targeting Liver Disease: TTR Amyloidosis

The liver has become an increasingly interesting target for oligonucleotide therapy. Mutations of the gene encoding transthyretin (TTR), expressed in vast amounts by the liver, result in a complex degenerative disease, termed familial amyloid polyneuropathy (FAP). Misfolded variants of TTR are linke...

Authors: Niemietz, Christoph
Chandhok, Gursimran
Schmidt, Hartmut
Division/Institute:FB 05: Medizinische Fakultät
Document types:Article
Media types:Text
Publication date:2015
Date of publication on miami:30.11.2015
Modification date:16.04.2019
Edition statement:[Electronic ed.]
Source:Molecules 20 (2015) 10, 17944-17975
Subjects:transthyretin; familial amyloid polyneuropathy; antisense oligonucleotide; small-interfering RNA; liver
DDC Subject:610: Medizin und Gesundheit
License:CC BY 4.0
Language:English
Notes:Finanziert durch den Open-Access-Publikationsfonds 2015/2016 der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF document
ISSN:1420-3049
URN:urn:nbn:de:hbz:6-47269568676
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-47269568676
Other Identifiers:DOI: 10.3390/molecules201017944
Digital documents:molecules-20-17944.pdf

The liver has become an increasingly interesting target for oligonucleotide therapy. Mutations of the gene encoding transthyretin (TTR), expressed in vast amounts by the liver, result in a complex degenerative disease, termed familial amyloid polyneuropathy (FAP). Misfolded variants of TTR are linked to the establishment of extracellular protein deposition in various tissues, including the heart and the peripheral nervous system. Recent progress in the chemistry and formulation of antisense (ASO) and small interfering RNA (siRNA) designed for a knockdown of TTR mRNA in the liver has allowed to address the issue of gene-specific molecular therapy in a clinical setting of FAP. The two therapeutic oligonucleotides bind to RNA in a sequence specific manner but exploit different mechanisms. Here we describe major developments that have led to the advent of therapeutic oligonucleotides for treatment of TTR-related disease.