Cargando…
Treatment of canine leukocyte adhesion deficiency by foamy virus vectors expressing CD18 from a PGK promoter
Proto-oncogene activation caused by retroviral vector integration can cause malignancies in gene therapy trials. This has led investigators to search for less genotoxic vectors with minimal enhancer activity and a decreased risk of influencing neighboring chromosomal gene expression after integratio...
Autores principales: | , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079787/ https://www.ncbi.nlm.nih.gov/pubmed/21228879 http://dx.doi.org/10.1038/gt.2010.169 |
_version_ | 1782202064486531072 |
---|---|
author | Bauer, Thomas R Olson, Erik M Huo, Yunwen Tuschong, Laura M Allen, James M Li, Yi Burkholder, Tanya H Russell, David W |
author_facet | Bauer, Thomas R Olson, Erik M Huo, Yunwen Tuschong, Laura M Allen, James M Li, Yi Burkholder, Tanya H Russell, David W |
author_sort | Bauer, Thomas R |
collection | PubMed |
description | Proto-oncogene activation caused by retroviral vector integration can cause malignancies in gene therapy trials. This has led investigators to search for less genotoxic vectors with minimal enhancer activity and a decreased risk of influencing neighboring chromosomal gene expression after integration. We previously showed that foamy virus vectors expressing the canine CD18 gene from an internal murine stem cell virus promoter could cure canine leukocyte adhesion deficiency. Here we have repeated these studies using a foamy virus vector expressing canine CD18 from a phosphoglycerate kinase gene promoter. In vitro analysis showed that this vector did not contain an enhancer that activated neighboring genes, and it expressed CD18 efficiently in canine neutrophils and CD34+ cells. However, dogs that received hematopoietic stem cells transduced with the PGK-CD18 vector continued to suffer from leukocyte adhesion deficiency, and sometimes died prematurely of the disease. These studies show that the phosphoglycerate kinase promoter cannot effectively replace the murine stem cell virus promoter in CD18-expressing foamy virus vectors, and they suggest that vectors containing a strong promoter/enhancer may be necessary for the treatment of human leukocyte adhesion deficiency. |
format | Text |
id | pubmed-3079787 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
record_format | MEDLINE/PubMed |
spelling | pubmed-30797872011-12-01 Treatment of canine leukocyte adhesion deficiency by foamy virus vectors expressing CD18 from a PGK promoter Bauer, Thomas R Olson, Erik M Huo, Yunwen Tuschong, Laura M Allen, James M Li, Yi Burkholder, Tanya H Russell, David W Gene Ther Article Proto-oncogene activation caused by retroviral vector integration can cause malignancies in gene therapy trials. This has led investigators to search for less genotoxic vectors with minimal enhancer activity and a decreased risk of influencing neighboring chromosomal gene expression after integration. We previously showed that foamy virus vectors expressing the canine CD18 gene from an internal murine stem cell virus promoter could cure canine leukocyte adhesion deficiency. Here we have repeated these studies using a foamy virus vector expressing canine CD18 from a phosphoglycerate kinase gene promoter. In vitro analysis showed that this vector did not contain an enhancer that activated neighboring genes, and it expressed CD18 efficiently in canine neutrophils and CD34+ cells. However, dogs that received hematopoietic stem cells transduced with the PGK-CD18 vector continued to suffer from leukocyte adhesion deficiency, and sometimes died prematurely of the disease. These studies show that the phosphoglycerate kinase promoter cannot effectively replace the murine stem cell virus promoter in CD18-expressing foamy virus vectors, and they suggest that vectors containing a strong promoter/enhancer may be necessary for the treatment of human leukocyte adhesion deficiency. 2011-01-13 2011-06 /pmc/articles/PMC3079787/ /pubmed/21228879 http://dx.doi.org/10.1038/gt.2010.169 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Bauer, Thomas R Olson, Erik M Huo, Yunwen Tuschong, Laura M Allen, James M Li, Yi Burkholder, Tanya H Russell, David W Treatment of canine leukocyte adhesion deficiency by foamy virus vectors expressing CD18 from a PGK promoter |
title | Treatment of canine leukocyte adhesion deficiency by foamy virus vectors expressing CD18 from a PGK promoter |
title_full | Treatment of canine leukocyte adhesion deficiency by foamy virus vectors expressing CD18 from a PGK promoter |
title_fullStr | Treatment of canine leukocyte adhesion deficiency by foamy virus vectors expressing CD18 from a PGK promoter |
title_full_unstemmed | Treatment of canine leukocyte adhesion deficiency by foamy virus vectors expressing CD18 from a PGK promoter |
title_short | Treatment of canine leukocyte adhesion deficiency by foamy virus vectors expressing CD18 from a PGK promoter |
title_sort | treatment of canine leukocyte adhesion deficiency by foamy virus vectors expressing cd18 from a pgk promoter |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3079787/ https://www.ncbi.nlm.nih.gov/pubmed/21228879 http://dx.doi.org/10.1038/gt.2010.169 |
work_keys_str_mv | AT bauerthomasr treatmentofcanineleukocyteadhesiondeficiencybyfoamyvirusvectorsexpressingcd18fromapgkpromoter AT olsonerikm treatmentofcanineleukocyteadhesiondeficiencybyfoamyvirusvectorsexpressingcd18fromapgkpromoter AT huoyunwen treatmentofcanineleukocyteadhesiondeficiencybyfoamyvirusvectorsexpressingcd18fromapgkpromoter AT tuschonglauram treatmentofcanineleukocyteadhesiondeficiencybyfoamyvirusvectorsexpressingcd18fromapgkpromoter AT allenjamesm treatmentofcanineleukocyteadhesiondeficiencybyfoamyvirusvectorsexpressingcd18fromapgkpromoter AT liyi treatmentofcanineleukocyteadhesiondeficiencybyfoamyvirusvectorsexpressingcd18fromapgkpromoter AT burkholdertanyah treatmentofcanineleukocyteadhesiondeficiencybyfoamyvirusvectorsexpressingcd18fromapgkpromoter AT russelldavidw treatmentofcanineleukocyteadhesiondeficiencybyfoamyvirusvectorsexpressingcd18fromapgkpromoter |