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Lentiviral vector-mediated gene transfer in adult mouse photoreceptors is impaired by the presence of a physical barrier

Gruter, O; Kostic, C; Crippa, SV; Perez, Maria Thereza LU ; Zografos, L; Schorderet, DF; Munier, FL and Arsenijevic, Y (2005) In Gene Therapy 12(11). p.942-947
Abstract
Gene transfer offers a substantial promise for the therapy of degenerative ocular diseases. Lentiviral vectors have the ability to efficiently transduce murine photoreceptors during the first days of life, but they are poorly effective on photoreceptors during adulthood. Here, we studied whether a physical barrier was responsible for this impairment. Previous studies have described the capacity of enzymes, such as chondroitinase ABC and neuraminidase X, to modify the structure of the interphotoreceptor matrix (IPM) when subretinally injected. Considering the IPM as a physical barrier that may decrease photoreceptor transduction, we injected different enzymes into the subretinal space of the adult mouse simultaneously with the lentiviral... (More)
Gene transfer offers a substantial promise for the therapy of degenerative ocular diseases. Lentiviral vectors have the ability to efficiently transduce murine photoreceptors during the first days of life, but they are poorly effective on photoreceptors during adulthood. Here, we studied whether a physical barrier was responsible for this impairment. Previous studies have described the capacity of enzymes, such as chondroitinase ABC and neuraminidase X, to modify the structure of the interphotoreceptor matrix (IPM) when subretinally injected. Considering the IPM as a physical barrier that may decrease photoreceptor transduction, we injected different enzymes into the subretinal space of the adult mouse simultaneously with the lentiviral vector preparation, to increase viral transduction by fragilizing the IPM. Subretinal injection of neuraminidase X and chondroitinase ABC induces modifications in the IPM by, respectively, revealing or decreasing peanut agglutinin sites on photoreceptors. The simultaneous subretinal injection of neuraminidase X with a lentiviral vector driving the expression of a reporter gene in the photoreceptors increases the number of transduced cells significantly ( around five-fold). After the enzyme treatment, the diffusion of the vector between the pigmented epithelium and the photoreceptors appears to facilitate the lentiviral vector transduction. Such approach targeting the IPM may help to design new strategies to improve gene delivery into the adult photoreceptors. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
lentivirus, gene transfer, retina, neuraminidase
in
Gene Therapy
volume
12
issue
11
pages
942 - 947
publisher
Nature Publishing Group
external identifiers
  • pmid:15772686
  • wos:000229297400011
  • scopus:20744444135
ISSN
0969-7128
DOI
10.1038/sj.gt.3302485
language
English
LU publication?
yes
id
11bed4ee-eb84-4ec0-bf25-69ade884df2f (old id 239060)
date added to LUP
2007-08-16 13:39:37
date last changed
2017-10-01 03:36:39
@article{11bed4ee-eb84-4ec0-bf25-69ade884df2f,
  abstract     = {Gene transfer offers a substantial promise for the therapy of degenerative ocular diseases. Lentiviral vectors have the ability to efficiently transduce murine photoreceptors during the first days of life, but they are poorly effective on photoreceptors during adulthood. Here, we studied whether a physical barrier was responsible for this impairment. Previous studies have described the capacity of enzymes, such as chondroitinase ABC and neuraminidase X, to modify the structure of the interphotoreceptor matrix (IPM) when subretinally injected. Considering the IPM as a physical barrier that may decrease photoreceptor transduction, we injected different enzymes into the subretinal space of the adult mouse simultaneously with the lentiviral vector preparation, to increase viral transduction by fragilizing the IPM. Subretinal injection of neuraminidase X and chondroitinase ABC induces modifications in the IPM by, respectively, revealing or decreasing peanut agglutinin sites on photoreceptors. The simultaneous subretinal injection of neuraminidase X with a lentiviral vector driving the expression of a reporter gene in the photoreceptors increases the number of transduced cells significantly ( around five-fold). After the enzyme treatment, the diffusion of the vector between the pigmented epithelium and the photoreceptors appears to facilitate the lentiviral vector transduction. Such approach targeting the IPM may help to design new strategies to improve gene delivery into the adult photoreceptors.},
  author       = {Gruter, O and Kostic, C and Crippa, SV and Perez, Maria Thereza and Zografos, L and Schorderet, DF and Munier, FL and Arsenijevic, Y},
  issn         = {0969-7128},
  keyword      = {lentivirus,gene transfer,retina,neuraminidase},
  language     = {eng},
  number       = {11},
  pages        = {942--947},
  publisher    = {Nature Publishing Group},
  series       = {Gene Therapy},
  title        = {Lentiviral vector-mediated gene transfer in adult mouse photoreceptors is impaired by the presence of a physical barrier},
  url          = {http://dx.doi.org/10.1038/sj.gt.3302485},
  volume       = {12},
  year         = {2005},
}