title: Chimeric rabies SADB19-VSVg-pseudotyped lentiviral vectors mediate long-range retrograde transduction from the mouse spinal cord.
abstract: Lentiviral vectors have proved an effective method to deliver transgenes into the brain; however, they are often hampered by a lack of spread from the site of injection. Modifying the viral envelope with a portion of a rabies envelope glycoprotein can enhance spread in the brain by using long-range axon projections to facilitate retrograde transport. In this study, we generated two chimeric envelopes containing the extra-virion and transmembrane domain of rabies SADB19 or CVS-N2c with the intra-virion domain of vesicular stomatitis virus. Viral particles were packaged containing a green fluorescent protein reporter construct under the control of the phosphoglycerokinase promoter. Both vectors produced high-titer particles with successful integration of the glycoproteins into the particle envelope and significant transduction of neurons in vitro. Injection of the SADB19 chimeric viral vector into the lumbar spinal cord of adult mice mediated a strong preference for gene transfer to local neurons and axonal terminals, with retrograde transport to neurons in the brainstem, hypothalamus and cerebral cortex. Development of this vector provides a useful means to reliably target select populations of neurons by retrograde targeting.
authors: 1] Department of Biochemistry, University of Otago, Dunedin, New Zealand [2] Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors: L
authors: L
authors: Schoderboeck
authors: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors: S
authors: S
authors: Riad
authors: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors: A M
authors: AM
authors: Bokor
authors: 1] Department of Biochemistry, University of Otago, Dunedin, New Zealand [2] Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
authors: H E
authors: HE
authors: Wicky
authors: 1] Otago Centre for Electron Microscopy, University of Otago, Dunedin, New Zealand [2] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
authors: M
authors: M
authors: Strauss
authors: 1] Otago Centre for Electron Microscopy, University of Otago, Dunedin, New Zealand [2] Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
authors: M
authors: M
authors: Bostina
authors: 1] Brain Health Research Centre, University of Otago, Dunedin, New Zealand [2] Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors: M J
authors: MJ
authors: Oswald
authors: 1] Brain Health Research Centre, University of Otago, Dunedin, New Zealand [2] Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
authors: R M
authors: RM
authors: Empson
authors: 1] Department of Biochemistry, University of Otago, Dunedin, New Zealand [2] Brain Health Research Centre, University of Otago, Dunedin, New Zealand [3] Genetics Otago, University of Otago, Dunedin, New Zealand.
authors: S M
authors: SM
authors: Hughes
mesh_terms: D000818:Animals; D001370:Axonal Transport; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D005991:Glycerol Kinase / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011820:Rabies virus / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism; D018116:Vesiculovirus / Q000235:genetics*; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D049452:Green Fluorescent Proteins; D005991:Glycerol Kinase
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