Assessment of viral and non-viral gene transfer into adult rat brains using HSV-1, calcium phosphate and PEI-based methods.
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.
Corso
Thomas D
TD
Molecular and Structural Neurobiology and Gene Therapy Program, SUNY, University at Buffalo, Buffalo, NY 14214, USA.
Torres
German
G
Goulah
Christopher
C
Roy
Indrajit
I
Gambino
Angelo S
AS
Nayda
John
J
Buckley
Timothy
T
Stachowiak
Ewa K
EK
Bergey
Earl J
EJ
Pudavar
Haridas
H
Dutta
Purnendu
P
Bloom
David C
DC
Bowers
William J
WJ
Stachowiak
Michal K
MK
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002130:Calcium Phosphates / Q000737:chemistry*; D002478:Cells, Cultured; D006224:Cricetinae; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human / Q000235:genetics*; D051379:Mice; D041681:NIH 3T3 Cells; D036103:Nanotechnology; D010300:Parkinson Disease / Q000209:etiology*; D011094:Polyethyleneimine / Q000737:chemistry*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism* / Q000821:virology; D014161:Transduction, Genetic / Q000379:methods
D002130:Calcium Phosphates; D017468:Receptors, Fibroblast Growth Factor; D011094:Polyethyleneimine; C020243:calcium phosphate; C496349:Fgfr1 protein, mouse; C496350:Fgfr1 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1