|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
14
|
|
pubmed:dateCreated |
2002-6-19
|
|
pubmed:abstractText |
The expression of reporter genes driven by the same human elongation factor 1alpha (EF1alpha) promoter in murine leukemia virus (MLV)- and human immunodeficiency virus type 1 (HIV-1)-based vectors was studied in either transfected or virally transduced cells. The HIV-1 vectors consistently expressed 3 to 10 times higher activity than the MLV vectors at both the RNA and protein levels. The difference was not attributable to transcriptional interference, alternative enhancer/silencer, or differential EF1alpha intron splicing. Based on nuclear run-on assays, both vectors exhibited similar EF1alpha transcriptional activity. The reduced RNA levels of MLV vectors could not be explained by the decrease in RNA half-lives. Southern analysis of proviral DNA indicated that both HIV-1 and MLV vectors efficiently propagated the EF1alpha intron in the transduced cells. To decipher the discrepancy in transgene expression between MLV and HIV-1 vectors, the role of RNA 3'-end processing was examined using a sensitive Cre/lox reporter assay. The results showed that MLV vectors, but not HIV-1 vectors, displayed high frequencies of readthrough of the 3' polyadenylation signal. Interestingly, the polyadenylation signal of a self-inactivating (SIN) HIV-1 vector was as leaky as that of the MLV vectors, suggesting a potential risk of oncogene activation by the lentiviral SIN vectors. Together, our results suggest that an efficient polyadenylation signal would improve both the efficacy and the safety of these vectors.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-10077624,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-10364378,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-10381536,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-10395555,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-10441560,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-10505094,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-10690406,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-10753827,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-10784449,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-10835679,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-11052933,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-11071633,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-11253666,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-11689654,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-12109139,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-1318403,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-1848693,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-1995416,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-1996111,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-2682638,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-2704078,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-2847958,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-2852891,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-2908926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-3033828,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-7498796,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-7552987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-7815539,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-8144559,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-8676491,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-8876144,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-8929910,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-9353246,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-9621037,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-9632380,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12072520-9847310
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jul
|
|
pubmed:issn |
0022-538X
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
76
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
7209-19
|
|
pubmed:dateRevised |
2009-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:12072520-Animals,
pubmed-meshheading:12072520-Genes, Reporter,
pubmed-meshheading:12072520-Genetic Vectors,
pubmed-meshheading:12072520-HIV-1,
pubmed-meshheading:12072520-Humans,
pubmed-meshheading:12072520-Introns,
pubmed-meshheading:12072520-Leukemia Virus, Murine,
pubmed-meshheading:12072520-Mice,
pubmed-meshheading:12072520-Peptide Elongation Factor 1,
pubmed-meshheading:12072520-Promoter Regions, Genetic,
pubmed-meshheading:12072520-RNA, Viral,
pubmed-meshheading:12072520-RNA 3' End Processing,
pubmed-meshheading:12072520-Safety,
pubmed-meshheading:12072520-Transcription, Genetic,
pubmed-meshheading:12072520-Transduction, Genetic,
pubmed-meshheading:12072520-Transfection,
pubmed-meshheading:12072520-Transgenes
|
|
pubmed:year |
2002
|
|
pubmed:articleTitle |
RNA 3' readthrough of oncoretrovirus and lentivirus: implications for vector safety and efficacy.
|
|
pubmed:affiliation |
Department of Molecular Genetics and Microbiology, Powell Gene Therapy Center and McKnight Brain Institute, University of Florida, Gainesville, Florida 32610-0266, USA.
|
|
pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Evaluation Studies
|
