Transduction patterns of pseudotyped lentiviral vectors in the nervous system.
We have developed a non-primate-based lentiviral vector based on the equine infectious anemia virus (EIAV) for efficient gene transfer to the central and peripheral nervous systems. Previously we have demonstrated that pseudotyping lentiviral vectors with the rabies virus glycoprotein confers retrograde axonal transport to these vectors. In the present study we have successfully produced high-titer EIAV vectors pseudotyped with envelope glycoproteins from Rhabdovirus vesicular stomatitis virus (VSV) serotypes (Indiana and Chandipura strains); rabies virus [various Evelyn-Rokitnicki-Abelseth ERA strains and challenge virus standard (CVS)]; Lyssavirus Mokola virus, a rabies-related virus; and Arenavirus lymphocytic choriomeningitis virus (LCMV). These vectors were delivered to the striatum or spinal cord of adult rats or muscle of neonatal mice by direct injection. We report that the lentiviral vectors pseudotyped with envelopes from the VSV Indiana strain, wild-type ERA, and CVS strains resulted in strong transduction in the striatum, while Mokola- and LCMV-pseudotyped vectors exhibited moderate and weak transduction, respectively. Furthermore ERA- and CVS-pseudotyped lentiviral vectors demonstrated retrograde transport and expression in distal neurons after injection in brain, spinal cord, and muscle. The differences in transduction efficiencies and retrograde transport conferred by these envelope glycoproteins present novel opportunities in designing therapeutic strategies for different neurological diseases.
Wong
Liang-Fong
LF
Neurobiology Group, Oxford Biomedica (UK) Ltd., Medawar Centre, Oxford OX4 4GA, United Kingdom. l.wong@oxfordbiomedica.co.uk
Azzouz
Mimoun
M
Walmsley
Lucy E
LE
Askham
Zoe
Z
Wilkes
Fraser J
FJ
Mitrophanous
Kyriacos A
KA
Kingsman
Susan M
SM
Mazarakis
Nicholas D
ND
D000818:Animals; D001692:Biological Transport; D003342:Corpus Striatum / Q000166:cytology; D015870:Gene Expression / Q000502:physiology; D015316:Genetic Therapy; D005822:Genetic Vectors; D006023:Glycoproteins / Q000378:metabolism; D004860:Infectious Anemia Virus, Equine / Q000235:genetics*; D007267:Injections; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics / Q000378:metabolism; D018114:Lyssavirus / Q000235:genetics; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal; D009420:Nervous System / Q000378:metabolism*; D009422:Nervous System Diseases / Q000628:therapy; D011820:Rabies virus / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism
D006023:Glycoproteins; D014759:Viral Envelope Proteins