Abstract
RNA interference has emerged as an innovative technology for gene silencing that degrades mRNAs complementary to the antisense strands of double-stranded, short interfering RNAs (siRNAs). Its therapeutic application has important advantages over small-molecule drugs since offers the possibility of targeting virtually all genes and allows selective silencing of one or several genes. So far, a relative small proportion of cellular proteins can bind and respond to chemical drugs. Based on that, RNA interference-mediated gene silencing is widely considered as a crucial breakthrough in molecular biology with a direct translation to medicine. The liver has been widely chosen as a model system for the development of RNA interference therapy due to the convenience and availability of effective delivery into this tissue. Numerous preclinical models have revealed promising results, but the safety of this technology remains the primary challenge in developing siRNA based treatments. Liver diseases comprise a broad spectrum of genetic and non-genetic pathologies including acute fulminant liver injury that demands urgent medical care, or chronic pathologies such as nonalcoholic fatty liver (NAFLD), alcoholic liver disease, liver cirrhosis, viral hepatitis and hepatocellular carcinoma (HCC). In some cases restoration of liver function is not possible and alternatives to liver transplantation offering novel and efficient therapeutic approaches are urgently needed. In this review, we describe recent insights on the advantages of using RNA interference in preclinical settings as a targeted strategy with potential to markedly improve the treatment of liver diseases.
Keywords: RNA interference, liver, acute liver failure, liver metabolism, fibrosis, hepatocellular carcinoma.
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