Title:RNA Interference as a Therapeutic Strategy for the Treatment of Liver Diseases
Volume: 21
Issue: 31
Author(s): Agueda Gonzalez-Rodriguez and Angela M. Valverde
Affiliation:
Keywords:
RNA interference, liver, acute liver failure, liver metabolism, fibrosis, hepatocellular carcinoma.
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.
