Production and characterization of a fusion peptide derived from the rabies virus glycoprotein (RVG29)

Protein Expr Purif. 2014 Dec:104:7-13. doi: 10.1016/j.pep.2014.09.001. Epub 2014 Sep 10.

Abstract

Gene therapy targeting the brain holds great promise in curing nervous system degenerative diseases in clinical applications. With this in mind, in a previous study a 29 amino-acid peptide derived from the rabies virus glycoprotein (RVG29) with a nonamer stretch of arginine residues (RVG29-9R) at its carboxy-terminus was exploited as a ligand for brain-targeting gene delivery. Importantly, the report demonstrated that the RVG29-9R vector was able to cross the blood-brain barrier. RVG29-9R is currently synthesized by commercial companies with high associated costs. In this study, in order to reduce the costs of producing RVG29-9R, we have expressed and purified 6mg of a recombinant peptide (RVG29-9R-6His) from 0.4g of cultured Escherichia coli. We assessed the physiochemical properties of RVG29-9R-6His, its cytotoxicity, and the in vitro transfection efficiency in Neuro 2a cells (which express the acetylcholine receptor). Our results reveal that the RVG29-9R-6His peptide recognized Neuro 2a cells in a dose-dependent manner and it was also able to bind plasmid DNA and deliver it into the Neuro 2a cells effectively. Therefore, our study has demonstrated that the recombinant RVG29-9R-6His peptide retains the functions of RVG29-9R and so may provide an economically viable and alternative production method for the manufacture of RVG29-9R.

Keywords: Brain; Gene delivery; RVG29-oligoarginine peptide; Rabies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival
  • DNA / administration & dosage
  • Glycoproteins / genetics*
  • Humans
  • Mice
  • Peptide Fragments / genetics*
  • Plasmids
  • Protein Stability
  • Rabies virus / metabolism*
  • Recombinant Fusion Proteins / genetics*
  • Recombinant Fusion Proteins / isolation & purification
  • Recombinant Fusion Proteins / toxicity
  • Viral Envelope Proteins / genetics*
  • Viral Proteins / genetics*

Substances

  • Glycoproteins
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Viral Envelope Proteins
  • Viral Proteins
  • rabies virus glycoprotein peptide
  • DNA