Therapeutic oligonucleotides targeting liver disease: TTR amyloidosis

Christoph Niemietz, Gursimran Chandhok, Hartmut Schmidt

Research output: Contribution to journalReview ArticleResearchpeer-review

22 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)17944-17975
Number of pages32
Issue number10
Publication statusPublished - 30 Sep 2015
Externally publishedYes


  • Antisense oligonucleotide
  • Familial amyloid polyneuropathy
  • Liver
  • Small-interfering RNA
  • Transthyretin

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