Advanced

Overexpression of Gibbon Ape Leukemia Virus (GALV) Receptor (GLVR1) on Human CD34(+) Cells Increases Gene Transfer Mediated by GALV Pseudotyped Vectors.

Relander, Thomas LU ; Brun, Ann LU ; Olsson, Karin LU ; Pedersen, Lene and Richter, Johan LU (2002) In Molecular Therapy 6(3). p.400-406
Abstract
Retroviral transduction of CD34(+) cells on Retronectin using gibbon ape leukemia virus (GALV) pseudotyped vectors is inhibited by high concentrations of vector containing medium (VCM). Furthermore, this inhibitory activity is stable for at least 48 hours at 37 degrees C and partially blocks a second hit with a GALV pseudotyped vector. We hypothesized that this inhibition was due to interference at the receptor level between infectious and noninfectious vector particles and that it might be possible to overcome it by increasing receptor expression on target cells. Activation of protein kinase C in CD34(+) cells with the phorbol ester PMA (phorbol 12-myristate 13-acetate) increased the mRNA level of the GALV receptor (GLVR1) and the... (More)
Retroviral transduction of CD34(+) cells on Retronectin using gibbon ape leukemia virus (GALV) pseudotyped vectors is inhibited by high concentrations of vector containing medium (VCM). Furthermore, this inhibitory activity is stable for at least 48 hours at 37 degrees C and partially blocks a second hit with a GALV pseudotyped vector. We hypothesized that this inhibition was due to interference at the receptor level between infectious and noninfectious vector particles and that it might be possible to overcome it by increasing receptor expression on target cells. Activation of protein kinase C in CD34(+) cells with the phorbol ester PMA (phorbol 12-myristate 13-acetate) increased the mRNA level of the GALV receptor (GLVR1) and the transduction efficiency (TE), and fully reversed the inhibition of transduction seen with high-titer GALV VCM. A murine stem cell virus (MSCV) vector with the GLVR1 receptor and green fluorescent protein cDNAs (MGLIG) was used to transduce fibroblasts, and clones expressing different levels of GLVR1 were isolated. The TE of these cells using a GALV vector correlated with the level of GLVR1 expression. When CD34(+) cells or K562 cells were first transduced with MGLIG and then with high-titer GALV VCM, no inhibition of transduction was seen. The low level of GLVR1 expression limits gene transfer to K562 and CD34(+) cells using GALV pseudotyped vectors, especially in the presence of high-titer VCMs. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Therapy
volume
6
issue
3
pages
400 - 406
publisher
Nature Publishing Group
external identifiers
  • pmid:12231177
  • wos:000177893600016
  • scopus:0036765230
ISSN
1525-0024
DOI
10.1006/mthe.2002.0678
language
English
LU publication?
yes
id
0158c406-adb3-4dd9-956b-3f1f68d2d1e1 (old id 110286)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12231177&dopt=Abstract
date added to LUP
2007-07-11 13:22:21
date last changed
2017-01-01 04:25:48
@article{0158c406-adb3-4dd9-956b-3f1f68d2d1e1,
  abstract     = {Retroviral transduction of CD34(+) cells on Retronectin using gibbon ape leukemia virus (GALV) pseudotyped vectors is inhibited by high concentrations of vector containing medium (VCM). Furthermore, this inhibitory activity is stable for at least 48 hours at 37 degrees C and partially blocks a second hit with a GALV pseudotyped vector. We hypothesized that this inhibition was due to interference at the receptor level between infectious and noninfectious vector particles and that it might be possible to overcome it by increasing receptor expression on target cells. Activation of protein kinase C in CD34(+) cells with the phorbol ester PMA (phorbol 12-myristate 13-acetate) increased the mRNA level of the GALV receptor (GLVR1) and the transduction efficiency (TE), and fully reversed the inhibition of transduction seen with high-titer GALV VCM. A murine stem cell virus (MSCV) vector with the GLVR1 receptor and green fluorescent protein cDNAs (MGLIG) was used to transduce fibroblasts, and clones expressing different levels of GLVR1 were isolated. The TE of these cells using a GALV vector correlated with the level of GLVR1 expression. When CD34(+) cells or K562 cells were first transduced with MGLIG and then with high-titer GALV VCM, no inhibition of transduction was seen. The low level of GLVR1 expression limits gene transfer to K562 and CD34(+) cells using GALV pseudotyped vectors, especially in the presence of high-titer VCMs.},
  author       = {Relander, Thomas and Brun, Ann and Olsson, Karin and Pedersen, Lene and Richter, Johan},
  issn         = {1525-0024},
  language     = {eng},
  number       = {3},
  pages        = {400--406},
  publisher    = {Nature Publishing Group},
  series       = {Molecular Therapy},
  title        = {Overexpression of Gibbon Ape Leukemia Virus (GALV) Receptor (GLVR1) on Human CD34(+) Cells Increases Gene Transfer Mediated by GALV Pseudotyped Vectors.},
  url          = {http://dx.doi.org/10.1006/mthe.2002.0678},
  volume       = {6},
  year         = {2002},
}