title: Therapeutic Oligonucleotides Targeting Liver Disease: TTR Amyloidosis.
abstract: 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.
authors.affiliation: Klinik für Transplantationsmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude A14, D-48149 Münster, Germany. christoph.niemietz@ukmuenster.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Niemietz
authors.affiliation: Klinik für Transplantationsmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude A14, D-48149 Münster, Germany. gursimran.chandhok@gmail.com.
authors.forename: Gursimran
authors.initials: G
authors.lastname: Chandhok
authors.affiliation: Klinik für Transplantationsmedizin, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude A14, D-48149 Münster, Germany. hepar@ukmuenster.de.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schmidt
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000235:genetics* / Q000628:therapy*; D000818:Animals; D000068456:Clinical Studies as Topic; D004353:Drug Evaluation, Preclinical; D020868:Gene Silencing; D015316:Genetic Therapy; D006801:Humans; D008107:Liver Diseases / Q000235:genetics* / Q000628:therapy*; D009154:Mutation; D009841:Oligonucleotides / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics* / Q000627:therapeutic use*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use; D011228:Prealbumin / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D011228:Prealbumin; D034741:RNA, Small Interfering
keywords: antisense oligonucleotide; familial amyloid polyneuropathy; liver; small-interfering RNA; transthyretin