Baculoviruses exhibit restricted cell type specificity in rat brain: a comparison of baculovirus- and adenovirus-mediated intracerebral gene transfer in vivo.
Baculoviruses have recently been shown to be effective gene transfer vectors in mammalian cells. However, very little information is available about their target cell tropism in the central nervous system. We studied transduction efficiency, tropism and biodistribution of baculoviruses after local delivery to rat brain and compared their properties to adenoviruses. It was found that baculoviruses specifically transduced cuboid epithelium of the choroid plexus in ventricles and that the transduction efficiency was as high as 76+/-14%, whereas adenoviruses showed preference to corpus callosum glial cells and ventricular ependymal lining. Only a modest microglia response was seen after the baculovirus transduction whereas the adenovirus gene transfer led to a strong microglia response. Sensitive nested RT-PCR revealed transgene expression in the hindbrain and in ectopic organs including spleen, heart and lung, which indicates that some escape of both vectors occurs to ectopic organs after local gene transfer to the brain. We conclude that both baculovirus and adenovirus vectors can be used for local intracerebral gene therapy. The knowledge of the cell type specificity of the vectors may offer a possibility to achieve targeted gene delivery to distinct brain areas. Baculoviruses seem to be especially useful for the targeting of choroid plexus cells.
Lehtolainen
P
P
AI Virtanen Institute and Gene Therapy Unit, Kuopio University Hospital, Finland.
Tyynelä
K
K
Kannasto
J
J
Airenne
K J
KJ
Ylä-Herttuala
S
S
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016367:Baculoviridae / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage*; D007150:Immunohistochemistry / Q000379:methods; D007763:Lac Operon; D008168:Lung / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012249:Rhombencephalon / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D014161:Transduction, Genetic / Q000379:methods