Abstract
While RNA has traditionally been viewed as a mechanism to transfer genetic information, its importance and functionality has only truly been demonstrated in the past 20 years. One prime example of this significance can be found within microRNAs (miRNAs), which are involved in the regulation of a substantial number of human genes. Consequently, these miRNAs represent a novel target for therapeutic agents towards the treatment of a variety of diseases and disorders. Specifically, misregulation of miR-122 has been demonstrated to be relevant in the cellular propagation of Hepatitis C (HCV), and thus modulators of miR-122 can have a substantial effect on viral loads. This protocol describes the development of an assay for the discovery of small molecule regulators of miR-122, and ultimately HCV therapeutics. Due to the excellent pharmacokinetic properties of small molecule libraries, these regulators represent a substantial advantage over traditional antisense agents.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Tomari Y, Zamore PD (2005) Perspective: machines for RNAi. Genes Dev 19:517
Deiters A (2010) Small molecule modifiers of the microRNA and RNA interference pathway. AAPS J 12:51
Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P (2005) Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 309:1577
Esquela-Kerscher A, Slack FJ (2006) Oncomirs – microRNAs with a role in cancer. Nat Rev Cancer 6:259
Lu J et al (2005) MicroRNA expression profiles classify human cancers. Nature 435:834
Chang J et al (2004) miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol 1(2):106–13
Castoldi M et al (2011) The liver-specific microRNA miR-122 controls systemic iron homeostasis in mice. J Clin Invest 121:1386
Elmén J et al (2008) LNA-mediated microRNA silencing in non-human primates. Nature 452:896
Lanford RE et al (2010) Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327:198
Young DD, Connelly C, Grohmann C, Deiters A (2010) Small molecule modifiers of MicroRNA miR-122 function for the treatment of hepatitis C virus infection and hepatocellular carcinoma. J Am Chem Soc 132:7976
Georgianna WE, Young DD (2011) Development and utilization of non-coding RNA-small molecule interactions. Org Biomol Chem 9:7969
Sambrook J, Russell DW (2011) Molecular cloning: a laboratory manual, 3rd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media, New York
About this protocol
Cite this protocol
Tripp, V.T., Young, D.D. (2014). Discovery of Small Molecule Modifiers of microRNAs for the Treatment of HCV Infection. In: Lafontaine, D., Dubé, A. (eds) Therapeutic Applications of Ribozymes and Riboswitches. Methods in Molecular Biology, vol 1103. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-730-3_12
Download citation
DOI: https://doi.org/10.1007/978-1-62703-730-3_12
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-729-7
Online ISBN: 978-1-62703-730-3
eBook Packages: Springer Protocols