Protecting neurons from HIV-1 gp120-induced oxidant stress using both localized intracerebral and generalized intraventricular administration of antioxidant enzymes delivered by SV40-derived vectors

Louboutin, Jean‐Pierre; Agrawal, Lokesh; Reyes, B. A. S.; Bockstaele, E. J. Van; Strayer, David S.

doi:10.1038/sj.gt.3303030

Cited by 37 publications

(52 citation statements)

References 65 publications

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“…12 Intracerebral injection of rSV40s carrying antioxidant enzymes, Cu/Zn superoxide dismutase (SOD1) or glutathione peroxidase (GPx1), SV(SOD1) or SV(GPx1), into the rat caudate putamen (CP), significantly protected neurons from apoptosis caused by injection of recombinant HIV-1 envelope glycoprotein, gp120 or Tat at the same location. [12][13][14] Moreover, intra-CP SV40-mediated gene delivery of antioxidant enzymes largely protected against several deleterious consequences elicited by injecting gp120 into the CP. [15][16][17] Vector administration into the lateral ventricle, particularly if preceded by mannitol intraperitoneal, protected from intra-CP gp120-induced neurotoxicity comparably to intra-CP vector administration.…”

Section: Introductionmentioning

confidence: 99%

Intracisternal rSV40 administration provides effective pan-CNS transgene expression

et al. 2011

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Potential genetic treatments for many generalized central nervous system (CNS) diseases require transgene expression throughout the CNS. Using oxidant stress and apoptosis caused by HIV-1 envelope gp120 as a model, we studied pan-CNS neuroprotective gene delivery into the cisterna magna (CM). Recombinant SV40 vectors carrying Cu/Zn superoxide dismutase or glutathione peroxidase were injected into rat CMs following intraperitoneal administration of mannitol. Sustained transgene expression was seen in neurons throughout the CNS. On challenge, 8 weeks later with gp120 injected into the caudate putamen, significant neuroprotection was documented. Thus, intracisternal administration of antioxidant-carrying rSV40 vectors may be useful in treating widespread CNS diseases such as HIV-1-associated neurocognitive disorders characterized by oxidative stress.

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Section: Introductionmentioning

confidence: 99%

Intracisternal rSV40 administration provides effective pan-CNS transgene expression

et al. 2011

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“…Since then, progress has been made in the use of polyomavirus capsid as a gene delivery vector. [18][19][20][21][22][23][24][25][26][27] However, the efficiency of gene transduction using polyomavirus vector is low. In part, this may have been caused by inefficient DNA packaging.…”

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confidence: 99%

Efficient gene transfer using the human JC virus-like particle that inhibits human colon adenocarcinoma growth in a nude mouse model

Chen

Wang

et al. 2010

Gene Ther

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“…21 Intracerebral or intraventricular injection of recombinant SV40 vectors carrying the antioxidant enzymes, Cu/Zn superoxide dismutase (SOD1) or glutathione peroxidase (GPx1), SV(SOD1) or SV(GPx1), significantly protected neurons from oxidative injury and apoptosis elicited by HIV-1 envelope glycoprotein, gp120 or Tat. [22][23][24][25] Intracerebroventricular administration of SV(SOD1) or SV(GPx1), particularly if preceded by systemic mannitol, is protected from local gp120-induced neurotoxicity as well as did intraparenchymal administration of antioxidant enzymes to the site of subsequent challenge (490% protection). 24 Previous personal reports from our group have shown the transduction efficiency and distribution of rSV40 viral vectors in the rodent brain.…”

Section: Expression Of Therapeutic Proteins May Be Useful In Treatingmentioning

confidence: 99%

“…[22][23][24][25] Intracerebroventricular administration of SV(SOD1) or SV(GPx1), particularly if preceded by systemic mannitol, is protected from local gp120-induced neurotoxicity as well as did intraparenchymal administration of antioxidant enzymes to the site of subsequent challenge (490% protection). 24 Previous personal reports from our group have shown the transduction efficiency and distribution of rSV40 viral vectors in the rodent brain. Few studies have been carried out using non-human primates.…”

Section: Expression Of Therapeutic Proteins May Be Useful In Treatingmentioning

confidence: 99%

“…21,22,24,57 After rehydration in 0.1 M PBS, pH 7.2, sections were treated with PBS plus 0.1% Triton X-100 10 min, washed twice for 5 min in PBS and then stained by NT (Molecular Probes Inc., Eugene, OR, USA) (1:100) for 20 min at room temperature. Sections were washed in PBS plus 0.1% Triton X-100, then 2Â with PBS and finally let to stand for 2 h at room temperature in PBS before being counterstained with 4¢,6-diamidino-2-phenylindole.…”

Section: Staining Of Neurons Using Neurotracementioning

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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Protecting neurons from HIV-1 gp120-induced oxidant stress using both localized intracerebral and generalized intraventricular administration of antioxidant enzymes delivered by SV40-derived vectors

Cited by 37 publications

References 65 publications

Intracisternal rSV40 administration provides effective pan-CNS transgene expression

Intracisternal rSV40 administration provides effective pan-CNS transgene expression

Efficient gene transfer using the human JC virus-like particle that inhibits human colon adenocarcinoma growth in a nude mouse model

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

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