Expression of brain-derived neurotrophic factor in the central nervous system of mice using a poliovirus-based vector.
Brain-derived neurotrophic factor (BDNF) is a promising candidate for the gene therapy of neurological disease. To deliver BDNF to neurons of the central nervous system (CNS), a nucleotide sequence encoding the mature peptide of BDNF was inserted into the genome of poliovirus, a neurotropic virus that is known to replicate mainly in motor neurons of the spinal cord of the CNS. Thus, the recombinant poliovirus constructed was replication-competent. The expression of BDNF in cultured cells infected with the recombinant poliovirus was evident when the cells were analyzed using an immunofluorescence assay and Western blotting. When the recombinant viruses were injected intramuscularly into transgenic mice that carry the human poliovirus receptor gene, the antigens of poliovirus and BDNF were detected in the motor neurons of the spinal cord at 3 days postinfection, and had disappeared by 7 days postinfection. This study suggests that poliovirus can be used as a virus vector for the delivery of neurotrophic factors to the motor neurons of the central nervous system and may provide a new approach for the treatment of motor neuron diseases.
Jia
Qingmei
Q
Department of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Liang
Fengyi
F
Ohka
Seii
S
Nomoto
Akio
A
Hashikawa
Tsutomu
T
D000818:Animals; D001483:Base Sequence; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D007273:Injections, Intramuscular; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000821:virology; D017955:Poliovirus / Q000235:genetics* / Q000254:growth & development; D011991:Receptors, Virus / Q000235:genetics; D014779:Virus Replication
D019208:Brain-Derived Neurotrophic Factor; D008565:Membrane Proteins; D011991:Receptors, Virus; C066100:poliovirus receptor