Therapeutic RNA manipulation in liver disease.
Posttranscriptional regulation of gene expression is increasingly recognized as a model for inherited and acquired disease. Recent work has expanded understanding of the range of mechanisms that regulate several of these distinct steps, including messenger RNA (mRNA) splicing, trafficking, and/or stability. Each of these pathways is implicated in disease pathogenesis, and each represents important avenues for therapeutic intervention. This review summarizes important mechanisms controlling mRNA processing and the regulation of mRNA degradation, including the role of microRNAs and RNA binding proteins. These pathways provide important opportunities for therapeutic targeting directed at splicing and degradation in order to attenuate genetic defects in RNA metabolism. We will highlight developments in vector development and validation for therapeutic manipulation of mRNA expression with a focus on potential applications in metabolic and immunomediated liver disease.
Kerr
Thomas A
TA
Division of Gastroenterology, Box 8124, Washington University School of Medicine, 660 Euclid Avenue, St. Louis, MO 63110, USA. nod@wustl.edu
Davidson
Nicholas O
NO
D015316:Genetic Therapy; D006801:Humans; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D012313:RNA / Q000235:genetics*; D012323:RNA Processing, Post-Transcriptional
D012313:RNA