Transduction Patterns of Pseudotyped Lentiviral Vectors in the Nervous System

• Published in: Molecular therapy Vol. 9; no. 1; pp. 101 - 111
• Main Authors: Wong, Liang-Fong, Azzouz, Mimoun, Walmsley, Lucy E, Askham, Zoe, Wilkes, Fraser J, Mitrophanous, Kyriacos A, Kingsman, Susan M, Mazarakis, Nicholas D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2004; Elsevier Limited
• Subjects: Anemia; Animals; Bats; Biological Transport; Corpus Striatum - cytology; Ebola virus; EIAV; Gene Expression - physiology; Gene therapy; Genetic Therapy; Genetic Vectors; Genomes; Glycoproteins; Glycoproteins - metabolism; HIV; Human immunodeficiency virus; Infectious Anemia Virus, Equine - genetics; Injections; lentivirus; Leukemia; Lymphocytic choriomeningitis virus - genetics; Lymphocytic choriomeningitis virus - metabolism; Lyssavirus - genetics; Male; Mice; Muscle, Skeletal; Nervous system; Nervous System - metabolism; Nervous System Diseases - therapy; Neurons; Neurosciences; Proteins; pseudotyping; Rabies; Rabies virus - genetics; Rabies virus - metabolism; Rats; Rats, Wistar; retrograde transport; Spinal Cord; Transduction, Genetic; Vectors (Biology); Viral Envelope Proteins - genetics; Viral Envelope Proteins - metabolism; Indiana; United Kingdom > UK; Zaire; United States > US; gene therapy; EIAV; retrograde transport; pseudotyping; lentivirus
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2003.09.017

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.