Linked Life Data

19632138

Source:http://linkedlifedata.com/resource/pubmed/id/19632138

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-8-11
pubmed:abstractText
Transgene expression shut-down, attenuation and/or variability from integrated retroviral vectors pose a major obstacle to gene therapy trials involving hematopoietic cells. We have undertaken a systematic assessment of the behavior of different configurations containing IFN-beta SAR and/or 5'HS4 beta-globin insulator sequences within a gammaretroviral vector optimized for high-level expression, focusing on the long-term achievement of stable, homogeneous transgene expression in the successfully transduced cells. Introduction of these cis regulatory elements did not perturb virus production and stability. Conversely, the SAR/5'HS4 insulator combination appeared to increase the homogeneity of EGFP expression in mass cultures. Furthermore, a clonal analysis of the dispersion of EGFP expression revealed that the IFN-SAR/5'HS4 insulator dyad was particularly effective in reducing the variability of transgene expression when both sequences were placed in opposite orientations within the retroviral backbone. These results may prove useful for the design of more stable retroviral expression cassettes able to counteract chromosomal position effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1096-0961
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
214-20
pubmed:meshHeading
pubmed:articleTitle
Boundary sequences stabilize transgene expression from subtle position effects in retroviral vectors.
pubmed:affiliation
Medical and Molecular Genetics Center, Institut d'Investigació Biomèdica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't