Epidermal growth factor targeting of bacteriophage to the choroid plexus for gene delivery to the central nervous system via cerebrospinal fluid.

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Epidermal growth factor targeting of bacteriophage to the choroid plexus for gene delivery to the central nervous system via cerebrospinal fluid. / Gonzalez, Ana; Leadbeater, Wendy; Podvin, S; Borboa, A; Burg, M; Sawada, R; Rayner, J; Sims, K; Terasaki, T; Johanson, C; Stopa, E; Eliceiri, B; Baird, Andrew.

In: Brain Research, Vol. 1359, 21.08.2010, p. 1-13.

Research output: Contribution to journalArticle

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Gonzalez, Ana ; Leadbeater, Wendy ; Podvin, S ; Borboa, A ; Burg, M ; Sawada, R ; Rayner, J ; Sims, K ; Terasaki, T ; Johanson, C ; Stopa, E ; Eliceiri, B ; Baird, Andrew. / Epidermal growth factor targeting of bacteriophage to the choroid plexus for gene delivery to the central nervous system via cerebrospinal fluid. In: Brain Research. 2010 ; Vol. 1359. pp. 1-13.

Bibtex

@article{0c007e1df31a4660ad0837d01bd1961a,
title = "Epidermal growth factor targeting of bacteriophage to the choroid plexus for gene delivery to the central nervous system via cerebrospinal fluid.",
abstract = "Because the choroid plexus normally controls the production and composition of cerebrospinal fluid and, as such, its many functions of the central nervous system, we investigated whether ligand-mediated targeting could deliver genes to its secretory epithelium. We show here that when bacteriophages are targeted with epidermal growth factor, they acquire the ability to enter choroid epithelial cells grown in vitro as cell cultures, ex vivo as tissue explants or in vivo by intracerebroventricular injection. The binding and internalization of these particles activate EGF receptors on targeted cells, and the dose- and time-dependent internalization of particles is inhibited by the presence of excess ligand. When the phage genome is further reengineered to contain like green fluorescent protein or firefly luciferase under control of the cytomegalovirus promoter, gene expression is detectable in the choroid plexus and ependymal epithelium by immunohistochemistry or by noninvasive imaging, respectively. Taken together, these data support the hypothesis that reengineered ligand-mediated gene delivery should be considered a viable strategy to increase the specificity of gene delivery to the central nervous system and bypass the blood-brain barrier so as to exploit the biological effectiveness of the choroid plexus as a portal of entry into the brain.",
keywords = "Gene delivery, Phage, Endocytosis, Cerebrospinal fluid, Epithelial cell, Epidermal growth factor",
author = "Ana Gonzalez and Wendy Leadbeater and S Podvin and A Borboa and M Burg and R Sawada and J Rayner and K Sims and T Terasaki and C Johanson and E Stopa and B Eliceiri and Andrew Baird",
year = "2010",
month = aug,
day = "21",
doi = "10.1016/j.brainres.2010.08.044",
language = "English",
volume = "1359",
pages = "1--13",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Epidermal growth factor targeting of bacteriophage to the choroid plexus for gene delivery to the central nervous system via cerebrospinal fluid.

AU - Gonzalez, Ana

AU - Leadbeater, Wendy

AU - Podvin, S

AU - Borboa, A

AU - Burg, M

AU - Sawada, R

AU - Rayner, J

AU - Sims, K

AU - Terasaki, T

AU - Johanson, C

AU - Stopa, E

AU - Eliceiri, B

AU - Baird, Andrew

PY - 2010/8/21

Y1 - 2010/8/21

N2 - Because the choroid plexus normally controls the production and composition of cerebrospinal fluid and, as such, its many functions of the central nervous system, we investigated whether ligand-mediated targeting could deliver genes to its secretory epithelium. We show here that when bacteriophages are targeted with epidermal growth factor, they acquire the ability to enter choroid epithelial cells grown in vitro as cell cultures, ex vivo as tissue explants or in vivo by intracerebroventricular injection. The binding and internalization of these particles activate EGF receptors on targeted cells, and the dose- and time-dependent internalization of particles is inhibited by the presence of excess ligand. When the phage genome is further reengineered to contain like green fluorescent protein or firefly luciferase under control of the cytomegalovirus promoter, gene expression is detectable in the choroid plexus and ependymal epithelium by immunohistochemistry or by noninvasive imaging, respectively. Taken together, these data support the hypothesis that reengineered ligand-mediated gene delivery should be considered a viable strategy to increase the specificity of gene delivery to the central nervous system and bypass the blood-brain barrier so as to exploit the biological effectiveness of the choroid plexus as a portal of entry into the brain.

AB - Because the choroid plexus normally controls the production and composition of cerebrospinal fluid and, as such, its many functions of the central nervous system, we investigated whether ligand-mediated targeting could deliver genes to its secretory epithelium. We show here that when bacteriophages are targeted with epidermal growth factor, they acquire the ability to enter choroid epithelial cells grown in vitro as cell cultures, ex vivo as tissue explants or in vivo by intracerebroventricular injection. The binding and internalization of these particles activate EGF receptors on targeted cells, and the dose- and time-dependent internalization of particles is inhibited by the presence of excess ligand. When the phage genome is further reengineered to contain like green fluorescent protein or firefly luciferase under control of the cytomegalovirus promoter, gene expression is detectable in the choroid plexus and ependymal epithelium by immunohistochemistry or by noninvasive imaging, respectively. Taken together, these data support the hypothesis that reengineered ligand-mediated gene delivery should be considered a viable strategy to increase the specificity of gene delivery to the central nervous system and bypass the blood-brain barrier so as to exploit the biological effectiveness of the choroid plexus as a portal of entry into the brain.

KW - Gene delivery

KW - Phage

KW - Endocytosis

KW - Cerebrospinal fluid

KW - Epithelial cell

KW - Epidermal growth factor

U2 - 10.1016/j.brainres.2010.08.044

DO - 10.1016/j.brainres.2010.08.044

M3 - Article

C2 - 20732308

VL - 1359

SP - 1

EP - 13

JO - Brain Research

JF - Brain Research

SN - 0006-8993

ER -