siRNAs encapsulated in recombinant capsid protein derived from Dengue serotype 2 virus inhibits the four serotypes of the virus and proliferation of cancer cells

J Biotechnol. 2015 Jan 10:193:23-33. doi: 10.1016/j.jbiotec.2014.11.003. Epub 2014 Nov 11.

Abstract

siRNA delivery potential of the Dengue virus capsid protein in cultured cells was recently reported, but target knockdown potential in the context of specific diseases has not been explored. In this study we have evaluated the utility of the protein as an siRNA carrier for anti Dengue viral and anti cancer applications using cell culture systems. We show that target specific siRNAs delivered using the capsid protein inhibit infection by the four serotypes of Dengue virus and proliferation of two cancer cell lines. Our data confirm the potential of the capsid for anti Dengue viral and anti cancer RNAi applications. In addition, we have optimized a fermentation strategy to improve the yield of Escherichia coli expressed D2C protein since the reported yields of E. coli expressed flaviviral capsid proteins are low.

Keywords: Aurorakinase; Capsid; Dengue; Rho A; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Aurora Kinase B / analysis
  • Aurora Kinase B / genetics
  • Aurora Kinase B / metabolism
  • Capsid Proteins / chemistry*
  • Capsid Proteins / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cricetinae
  • Dengue / virology
  • Dengue Virus / drug effects
  • Dengue Virus / genetics*
  • Drug Carriers
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Host-Pathogen Interactions / drug effects
  • Humans
  • Mice
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / pharmacology*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology*

Substances

  • Antigens, Viral
  • Antineoplastic Agents
  • Antiviral Agents
  • Capsid Proteins
  • Drug Carriers
  • RNA, Small Interfering
  • Recombinant Proteins
  • Aurora Kinase B