Intraperitoneal inoculation of Sandhoff mouse neonates with an HIV-1 based lentiviral vector exacerbates the attendant neuroinflammation and disease phenotype

Stephanos Kyrkanides; Jen nie H. Miller; Ross H. Tallents; Sabine M. Brouxhon; Gina M. Centola; John A. Olschowka

doi:10.1016/j.jneuroim.2007.05.010

Intraperitoneal inoculation of Sandhoff mouse neonates with an HIV-1 based lentiviral vector exacerbates the attendant neuroinflammation and disease phenotype

Stephanos Kyrkanides, Jen nie H. Miller, Ross H. Tallents, Sabine M. Brouxhon, Gina M. Centola, John A. Olschowka

Oral Health Science

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

We aimed to evaluate the efficacy of VSV-G pseudotyped, defective HIV-1 based lentiviral vectors for the neonatal transfer of therapeutic genes following systemic administration in Sandhoff mouse pups. Despite transgene expression in mouse brains, these animals presented with significant exacerbation and acceleration of the disease neurological phenotype. We observed an increase and acceleration in the presence of MHC-II and CD45+ cells in their brains, along with neuroinflammation, but not in control heterozygous or wild type littermates that also received the same treatment.

Original language	English
Pages (from-to)	39-47
Number of pages	9
Journal	Journal of Neuroimmunology
Volume	188
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jneuroim.2007.05.010
State	Published - Aug 2007

Bibliographical note

Funding Information:
We would like to thank Dr. Richard L. Proia for providing the HexB −/− knockout Sandhoff mice as well as the goat anti-HEXB antibody used in this study. This work was supported in part by a grant from NIH/NINDS number NS048339 awarded to SK.

Keywords

Gene therapy
Lentiviral vectors
Lysosomal storage disorder
Sandhoff disease
β-hexosaminidase

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Neurology
Clinical Neurology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jneuroim.2007.05.010

Cite this

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title = "Intraperitoneal inoculation of Sandhoff mouse neonates with an HIV-1 based lentiviral vector exacerbates the attendant neuroinflammation and disease phenotype",

abstract = "We aimed to evaluate the efficacy of VSV-G pseudotyped, defective HIV-1 based lentiviral vectors for the neonatal transfer of therapeutic genes following systemic administration in Sandhoff mouse pups. Despite transgene expression in mouse brains, these animals presented with significant exacerbation and acceleration of the disease neurological phenotype. We observed an increase and acceleration in the presence of MHC-II and CD45+ cells in their brains, along with neuroinflammation, but not in control heterozygous or wild type littermates that also received the same treatment.",

keywords = "Gene therapy, Lentiviral vectors, Lysosomal storage disorder, Sandhoff disease, β-hexosaminidase",

author = "Stephanos Kyrkanides and Miller, {Jen nie H.} and Tallents, {Ross H.} and Brouxhon, {Sabine M.} and Centola, {Gina M.} and Olschowka, {John A.}",

note = "Funding Information: We would like to thank Dr. Richard L. Proia for providing the HexB −/− knockout Sandhoff mice as well as the goat anti-HEXB antibody used in this study. This work was supported in part by a grant from NIH/NINDS number NS048339 awarded to SK.",

year = "2007",

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doi = "10.1016/j.jneuroim.2007.05.010",

language = "English",

volume = "188",

pages = "39--47",

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T1 - Intraperitoneal inoculation of Sandhoff mouse neonates with an HIV-1 based lentiviral vector exacerbates the attendant neuroinflammation and disease phenotype

AU - Kyrkanides, Stephanos

AU - Miller, Jen nie H.

AU - Tallents, Ross H.

AU - Brouxhon, Sabine M.

AU - Centola, Gina M.

AU - Olschowka, John A.

N1 - Funding Information: We would like to thank Dr. Richard L. Proia for providing the HexB −/− knockout Sandhoff mice as well as the goat anti-HEXB antibody used in this study. This work was supported in part by a grant from NIH/NINDS number NS048339 awarded to SK.

PY - 2007/8

Y1 - 2007/8

N2 - We aimed to evaluate the efficacy of VSV-G pseudotyped, defective HIV-1 based lentiviral vectors for the neonatal transfer of therapeutic genes following systemic administration in Sandhoff mouse pups. Despite transgene expression in mouse brains, these animals presented with significant exacerbation and acceleration of the disease neurological phenotype. We observed an increase and acceleration in the presence of MHC-II and CD45+ cells in their brains, along with neuroinflammation, but not in control heterozygous or wild type littermates that also received the same treatment.

AB - We aimed to evaluate the efficacy of VSV-G pseudotyped, defective HIV-1 based lentiviral vectors for the neonatal transfer of therapeutic genes following systemic administration in Sandhoff mouse pups. Despite transgene expression in mouse brains, these animals presented with significant exacerbation and acceleration of the disease neurological phenotype. We observed an increase and acceleration in the presence of MHC-II and CD45+ cells in their brains, along with neuroinflammation, but not in control heterozygous or wild type littermates that also received the same treatment.

KW - Gene therapy

KW - Lentiviral vectors

KW - Lysosomal storage disorder

KW - Sandhoff disease

KW - β-hexosaminidase

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SN - 0165-5728

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JF - Journal of Neuroimmunology

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Intraperitoneal inoculation of Sandhoff mouse neonates with an HIV-1 based lentiviral vector exacerbates the attendant neuroinflammation and disease phenotype

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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