HSV-1 VP22 augments adenoviral gene transfer to CNS neurons in the retina and striatum in vivo.
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.
Kretz
A
A
Department of Neurology, Neuroregeneration Laboratory, Tübingen, Germany.
Wybranietz
W A
WA
Hermening
S
S
Lauer
U M
UM
Isenmann
S
S
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006801:Humans; D007111:Immunity, Cellular; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000821:virology; D010750:Phosphoproteins / Q000235:genetics; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012160:Retina / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D014161:Transduction, Genetic; D015678:Viral Structural Proteins / Q000235:genetics*
D008164:Luminescent Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D015678:Viral Structural Proteins; C073413:herpes simplex virus type 1 protein VP22; D049452:Green Fluorescent Proteins