Source:http://linkedlifedata.com/resource/pubmed/id/12411297
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions |
umls-concept:C0017033,
umls-concept:C0017337,
umls-concept:C0086022,
umls-concept:C0086418,
umls-concept:C0271979,
umls-concept:C0330390,
umls-concept:C0348011,
umls-concept:C0442335,
umls-concept:C0542560,
umls-concept:C0591833,
umls-concept:C1705099,
umls-concept:C1705822,
umls-concept:C1707513,
umls-concept:C1947976,
umls-concept:C2350240
|
| pubmed:issue |
6
|
| pubmed:dateCreated |
2003-2-28
|
| pubmed:abstractText |
Increased fetal hemoglobin (HbF) levels diminish the clinical severity of beta-thalassemia and sickle cell anemia. A treatment strategy using autologous stem cell-targeted gene transfer of a gamma-globin gene may therefore have therapeutic potential. We evaluated oncoretroviral- and lentiviral-based gamma-globin vectors for expression in transduced erythroid cell lines. Compared with gamma-globin, oncoretroviral vectors containing either a beta-spectrin or beta-globin promoter and the alpha-globin HS40 element, a gamma-globin lentiviral vector utilizing the beta-globin promoter and elements from the beta-globin locus control region demonstrated a higher probability of expression. This lentiviral vector design was evaluated in lethally irradiated mice that received transplants of transduced bone marrow cells. Long-term, stable erythroid expression of human gamma-globin was observed with levels of vector-encoded gamma-globin mRNA ranging from 9% to 19% of total murine alpha-globin mRNA. The therapeutic efficacy of the vector was subsequently evaluated in a murine model of beta-thalassemia intermedia. The majority of mice that underwent transplantation expressed significant levels of chimeric m(alpha)(2)h(gamma)(2) molecules (termed HbF), the amount of which correlated with the degree of phenotypic improvement. A group of animals with a mean HbF level of 21% displayed a 2.5 g/dL (25 g/L) improvement in Hb concentration and normalization of erythrocyte morphology relative to control animals. gamma-Globin expression and phenotypic improvement was variably lower in other animals due to differences in vector copy number and chromosomal position effects. These data establish the potential of using a gamma-globin lentiviral vector for gene therapy of beta-thalassemia.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
0006-4971
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
101
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2175-83
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:12411297-Animals,
pubmed-meshheading:12411297-Bone Marrow Cells,
pubmed-meshheading:12411297-Bone Marrow Transplantation,
pubmed-meshheading:12411297-Erythrocytes,
pubmed-meshheading:12411297-Fetal Hemoglobin,
pubmed-meshheading:12411297-Gene Expression,
pubmed-meshheading:12411297-Gene Therapy,
pubmed-meshheading:12411297-Genetic Vectors,
pubmed-meshheading:12411297-Globins,
pubmed-meshheading:12411297-Humans,
pubmed-meshheading:12411297-Lentivirus,
pubmed-meshheading:12411297-Leukemia, Erythroblastic, Acute,
pubmed-meshheading:12411297-Mice,
pubmed-meshheading:12411297-Mice, Knockout,
pubmed-meshheading:12411297-Phenotype,
pubmed-meshheading:12411297-RNA, Messenger,
pubmed-meshheading:12411297-Retroviridae,
pubmed-meshheading:12411297-Spleen,
pubmed-meshheading:12411297-Transfection,
pubmed-meshheading:12411297-Tumor Cells, Cultured,
pubmed-meshheading:12411297-beta-Thalassemia
|
| pubmed:year |
2003
|
| pubmed:articleTitle |
The degree of phenotypic correction of murine beta -thalassemia intermedia following lentiviral-mediated transfer of a human gamma-globin gene is influenced by chromosomal position effects and vector copy number.
|
| pubmed:affiliation |
Division of Experimental Hematology, Department of Hematology and Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA. derek.persons@stjude.org
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|