Lentiviral Gene Transfer to the Nonhuman Primate Brain

Kordower, Jeffrey H.; Bloch, Jocelyne; Yang, Shuang; Chu, Yaping; Palfi, Stéphane; Roitberg, Ben; Emborg, Marina E.; Hantraye, Philippe; Déglon, Nicole; Aebischer, Patrick

doi:10.1006/exnr.1999.7178

Cited by 199 publications

(125 citation statements)

References 31 publications

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“…13,14 In terms of an HIV-1-based lentiviral system, the preferential tropism of VSVG pseudotyped virus for neurons has been previously observed in rodents 15,16 and non-human primates. 17 However, when injected specifically into white matter cells of all major macroglial types are transduced. 18 Consistent with these studies, transduction patterns in corpus striatum in adult rats showed that VSVG and rabies pseudotyped NILV preferentially transduce neurons.…”

Section: Efficient Gene Delivery To Adult and Fetal Cnsmentioning

confidence: 99%

Efficient gene delivery to the adult and fetal CNS using pseudotyped non-integrating lentiviral vectors

et al. 2009

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Non-integrating lentiviral vectors show considerable promise for gene therapy applications as they persist as long-term episomes in non-dividing cells and diminish risks of insertional mutagenesis. In this study, non-integrating lentiviral vectors were evaluated for their use in the adult and fetal central nervous system of rodents. Vectors differentially pseudotyped with vesicular stomatitis virus, rabies and baculoviral envelope proteins allowed targeting of varied cell populations. Efficient gene delivery to discrete areas of the brain and spinal cord was observed following stereotactic administration. Furthermore, after direct in utero administration (E14), sustained and strong expression was observed 4 months into adulthood. Quantification of transduction and viral copy number was comparable when using nonintegrating lentivirus and conventional integrating vector. These data support the use of non-integrating lentiviral vectors as an effective alternative to their integrating counterparts in gene therapy applications, and highlight their potential for treatment of inherited and acquired neurological disorders.

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Section: Efficient Gene Delivery To Adult and Fetal Cnsmentioning

confidence: 99%

Efficient gene delivery to the adult and fetal CNS using pseudotyped non-integrating lentiviral vectors

et al. 2009

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“…Moreover, several vector injections were carried out in the same structure in some of these studies. 32,42 In this study, a single injection of 10 8 rSV40 vectors transduced between 1 500 000 and 1 800 000 cells, almost all of them neurons, in the caudate nucleus, respectively, 1 and 6 months after injection.…”

Section: Discussionmentioning

confidence: 66%

“…Gene transfer to the rodent and primate CNS in vivo has been shown with lentiviral vectors derived from HIV and other lentiviruses. 3,4,8,[42][43][44] HSV type 1 multigene vector safety and biodistribution have also been studied in non-human primate brain. 45 In non-human primates, CNS transduction efficiency and durability varied with the vector, injection site and method of delivery.…”

Section: Discussionmentioning

confidence: 99%

“…45 In non-human primates, CNS transduction efficiency and durability varied with the vector, injection site and method of delivery. For AAV vectors, transduced cells numbered from 444 400 at 8 weeks to 1 296 350 at 3 years, 32 for lentiviral vectors, 764 149 at 1 month for lentiviral vectors 42 titers ranging between 2.75Â10 12 genome copies per ml for AAV2/1, 1.69Â10 13 42 and between 2Â10 10 PFU ml À1 (ref. 30) and 2Â10 9 PFU ml À1 (ref.…”

Section: Discussionmentioning

confidence: 99%

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Gene transfer to the rhesus monkey brain using SV40-derived vectors is durable and safe

et al. 2011

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Gene transfer to central nervous system (CNS) has been approached using various vectors. Recombinant SV40-derived vectors (rSV40s) transduce human neurons and microglia effectively in vitro and in rodent brains in vivo, so we tested rSV40s gene transfer to rhesus monkey CNS in vivo, to characterize the distribution, duration and safety of such gene delivery. We used rSV40s carrying HIV-1 RevM10 with a carboxyl-terminal AU1 epitope tag as a marker, and others with the antioxidant enzymes, Cu/Zn superoxide dismutase and glutathione peroxidase. Vectors were injected stereotaxically into the caudate nucleus. Transgene expression was studied at 1 and 6 months by immunostaining serial brain sections. After intraparenchymal administration, numerous transgene-expressing cells were seen, with a longitudinal extent of 20 mm. In neurons and, more rarely, microglial cells, transgene expression remained strong throughout the 6-month study period. Astrocytes and oligodendroglia were not transduced. No evidence of inflammation or tissue damage was observed. SV40-derived vectors may thus be useful for long-term gene expression in the monkey brain and, potentially, in the human brain.

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“…Lentiviral vectors are ideal candidates for such gene delivery tools, since they have been shown to transduce dividing as well as nondividing cells, resulting in stable integration and long-term expression of the transgene. [1][2][3][4] The tropism of lentiviruses is determined in part by the interaction of the viral surface glycoproteins with receptor molecules expressed on the cell surface, and this can be modified by the incorporation of heterologous glycoproteins derived from other enveloped viruses. 5 This phenomenon, referred to as pseudotyping, can be used to achieve selective entry into specific target cells by taking advantage of the natural tropism of heterologous envelope proteins, and can thereby increase the efficiency and safety during in vivo transfer of various therapeutic agents.…”

Section: Introductionmentioning

confidence: 99%

Simian immunodeficiency virus vector pseudotypes differ in transduction efficiency and target cell specificity in brain

et al. 2007

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Lentiviral Gene Transfer to the Nonhuman Primate Brain

Cited by 199 publications

References 31 publications

Efficient gene delivery to the adult and fetal CNS using pseudotyped non-integrating lentiviral vectors

Efficient gene delivery to the adult and fetal CNS using pseudotyped non-integrating lentiviral vectors

Gene transfer to the rhesus monkey brain using SV40-derived vectors is durable and safe

Simian immunodeficiency virus vector pseudotypes differ in transduction efficiency and target cell specificity in brain

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