open access

Vol 64, No 3 (2005)
ORIGINAL ARTICLES
Published online: 2005-06-22
Submitted: 2012-02-06
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Assessment of viral and non-viral gene transfer into adult rat brains using HSV-1, calcium phosphate and PEI-based methods

Thomas D. Corso, German Torres, Christopher Goulah, Indrajit Roy, Angelo S. Gambino, John Nayda, Timothy Buckley, Ewa K. Stachowiak, Earl J. Bergey, Haridas Pudavar, Purnendu Dutta, David C. Bloom, William J. Bowers, Michal K. Stachowiak
Folia Morphol 2005;64(3):130-144.

open access

Vol 64, No 3 (2005)
ORIGINAL ARTICLES
Published online: 2005-06-22
Submitted: 2012-02-06

Abstract

CNS gene transfer could provide new approaches to the modelling of neurodegenerative diseases and devising potential therapies. One such disorder is Parkinson’s disease (PD), in which dysfunction of several different metabolic processes has been implicated. Here we review the literature on gene transfer systems based on herpes simplex virus type 1 (HSV-1) and non-viral polyethyleneimine (PEI) and calcium phosphate nanoparticle methods. We also assess the usefulness of various CNS gene delivery methods and present some of our own data to exemplify such usefulness. Our data result from vectors stereotaxically introduced to the substantia nigra (SN) of adult rats and evaluated 1 week and/or 1 month post injection using histochemical methods to assess recombinant ß-galactosidase enzyme activity. Gene transfer using PEI or calcium phosphate-mediated transfections was observed for both methods and PEI was comparable to that of HSV-1 amplicon. Our data show that the amplicon delivery was markedly increased when packaged with a helper virus and was similar to the expression profile achieved with a full-size replication-defective HSV-1 recombinant (8117/43). We also examine whether PEI or HSV-1 amplicon-mediated gene transfer could facilitate assessment of the biological effects induced by a dominant negative FGF receptor-1 mutant to model the reduced FGF signalling thought to occur in Parkinson’s disease.

Abstract

CNS gene transfer could provide new approaches to the modelling of neurodegenerative diseases and devising potential therapies. One such disorder is Parkinson’s disease (PD), in which dysfunction of several different metabolic processes has been implicated. Here we review the literature on gene transfer systems based on herpes simplex virus type 1 (HSV-1) and non-viral polyethyleneimine (PEI) and calcium phosphate nanoparticle methods. We also assess the usefulness of various CNS gene delivery methods and present some of our own data to exemplify such usefulness. Our data result from vectors stereotaxically introduced to the substantia nigra (SN) of adult rats and evaluated 1 week and/or 1 month post injection using histochemical methods to assess recombinant ß-galactosidase enzyme activity. Gene transfer using PEI or calcium phosphate-mediated transfections was observed for both methods and PEI was comparable to that of HSV-1 amplicon. Our data show that the amplicon delivery was markedly increased when packaged with a helper virus and was similar to the expression profile achieved with a full-size replication-defective HSV-1 recombinant (8117/43). We also examine whether PEI or HSV-1 amplicon-mediated gene transfer could facilitate assessment of the biological effects induced by a dominant negative FGF receptor-1 mutant to model the reduced FGF signalling thought to occur in Parkinson’s disease.
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Keywords

Parkinson’s disease; fibroblast growth factor; substantia nigra; gene transfection; herpes simplex virus-1; polyethyleneimine; calcium phosphate nanoparticle; tyrosine kinase; adenovirus; ß-galactosidase

About this article
Title

Assessment of viral and non-viral gene transfer into adult rat brains using HSV-1, calcium phosphate and PEI-based methods

Journal

Folia Morphologica

Issue

Vol 64, No 3 (2005)

Pages

130-144

Published online

2005-06-22

Bibliographic record

Folia Morphol 2005;64(3):130-144.

Keywords

Parkinson’s disease
fibroblast growth factor
substantia nigra
gene transfection
herpes simplex virus-1
polyethyleneimine
calcium phosphate nanoparticle
tyrosine kinase
adenovirus
ß-galactosidase

Authors

Thomas D. Corso
German Torres
Christopher Goulah
Indrajit Roy
Angelo S. Gambino
John Nayda
Timothy Buckley
Ewa K. Stachowiak
Earl J. Bergey
Haridas Pudavar
Purnendu Dutta
David C. Bloom
William J. Bowers
Michal K. Stachowiak

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