The mRVG-9R peptide as a potential therapeutic vector to the central nervous system cells

Cell Biol Int. 2019 Jul;43(7):809-819. doi: 10.1002/cbin.11161. Epub 2019 May 21.

Abstract

Our research group has developed a cell-penetrating peptide-based delivery system that includes the Asn194Lys mutation in the rabies virus glycoprotein-9R peptide (mRVG-9R). This system has the capacity to deliver DNA in astrocytes and SH-SY5Y cells. The aim of this study was to evaluate the ability of the mRVG-9R peptide to deliver DNA molecules to murine brain cells. The mRVG-9R peptide, a karyophilic peptide (KP) and a plasmid encoding green fluorescent protein (GFP) were bound by electrostatic charges to form the mRVG-9R complex. mRVG-9R complex was injected into the cerebral cortex, striatum and hippocampus of C57BL/6 mice by stereotactic surgery. After 2, 4, and 20 days, the animals were sacrificed and their brains were prepared for quantitative reverse-transcription polymerase chain reaction and histological analysis. We detected the GFP expression in neurons and glial cells in the cerebral cortex, striatum, and hippocampus of the murine brain. The results suggest that the mRVG-9R peptide has the ability to deliver DNA molecules to murine brain cells. Also, the expression of the reporter gene is maintained at least up to 20 days after injection in neurons, astrocytes, oligodendrocytes, and microglia cells. Thus, the in vivo transfection ability of the mRVG-9R peptide, makes it a promising candidate as a therapeutic gene delivery vector to the central nervous system cells.

Keywords: CPPs; astrocytes; mRVG-9R; microglia; oligodendrocytes; therapeutic vector.

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Cell-Penetrating Peptides / pharmacology*
  • Corpus Striatum / cytology
  • Corpus Striatum / drug effects*
  • Drug Carriers / pharmacology*
  • Genes, Reporter
  • Genetic Vectors / therapeutic use
  • Glycoproteins / pharmacology*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism*
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Microglia / cytology
  • Neurons / cytology
  • Neurons / drug effects
  • Oligodendroglia / cytology
  • Oligodendroglia / drug effects
  • Peptide Fragments / pharmacology*
  • Transfection / methods
  • Viral Proteins / pharmacology*

Substances

  • Cell-Penetrating Peptides
  • Drug Carriers
  • Glycoproteins
  • Peptide Fragments
  • Viral Proteins
  • rabies virus glycoprotein peptide
  • Green Fluorescent Proteins

Grants and funding