HSV-1 VP22 augments adenoviral gene transfer to CNS neurons in the retina and striatum in vivo

Mol Ther. 2003 May;7(5 Pt 1):659-69. doi: 10.1016/s1525-0016(03)00062-5.

Abstract

One of the obstacles to efficient vector-mediated gene transfer to the CNS is limited transduction of target neurons. The VP22 tegument protein of HSV-1 can cross biological membranes and translocate the VP22 protein from primarily transfected cells to many surrounding cells in vitro. Here, we employed an adenoviral vector coding for a VP22-GFP fusion protein driven by a CMV promoter to test its capability of transducing CNS neurons in vivo. Intraocular administration of Ad.VP22-GFP in the rat doubled both the retinal area containing transduced, GFP-expressing cells and the absolute number of GFP-expressing retinal neurons compared to Ad.GFP transduction. Following injection of Ad.VP22-GFP into the mouse brain, the transduced striatal area was increased by a factor of 7 compared to intracerebral injection of Ad.GFP. In both retina and striatum, GFP-expressing cells were identified as mainly neurons. Thus, VP22 greatly augments adenovirus-mediated transgene delivery to CNS neuronsin vivo, making VP22 a promising tool for enhancing the efficacy of adenoviral gene transfer of protective factors to the CNS.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Corpus Striatum / cytology
  • Corpus Striatum / metabolism*
  • Corpus Striatum / virology
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Genetic Vectors*
  • Green Fluorescent Proteins
  • Humans
  • Immunity, Cellular
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / virology
  • Phosphoproteins / genetics
  • Protein Transport
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins / genetics
  • Retina / cytology
  • Retina / metabolism*
  • Retina / virology
  • Transduction, Genetic
  • Viral Structural Proteins / genetics*

Substances

  • Luminescent Proteins
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • Viral Structural Proteins
  • herpes simplex virus type 1 protein VP22
  • Green Fluorescent Proteins