Linked Life Data

11358353

Source:http://linkedlifedata.com/resource/pubmed/id/11358353

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2001-5-18
pubmed:abstractText
Increased expression of fetal hemoglobin can ameliorate the clinical severity of sickle cell disease. Whereas temporary induction of fetal hemoglobin can be achieved by pharmacologic therapy, gene transfer resulting in high-level expression of the fetal gamma-globin gene may provide a permanent cure for sickle cell disease. We had previously developed a high-titer, genetically stable retroviral vector in which the human gamma-globin gene was linked to HS-40, the major regulatory element of the human alpha-globin gene cluster. Based on experience in transgenic mice, the truncated promoter of the gamma-globin gene of this vector should be active in adult erythroid cells. Our earlier studies demonstrated that this retroviral vector can give rise to high-level expression of the human gamma-globin gene in murine erythroleukemia (MEL) cells. We have now utilized this vector to transduce murine bone marrow cells that were transplanted into W/W(v) recipient mice. Analysis of transduction of murine BFU-e's in vitro and peripheral blood cells from transplanted mice in vivo demonstrated efficient transfer of the human gamma-globin gene. However, in contrast to the high level of expression of the human gamma-globin gene of this vector in MEL cells, the gene was completely silent in vivo in all transplanted mice. These observations confirm that all the necessary regulatory elements responsible for the developmental stage-specific expression of the human gamma-globin gene reside in its proximal sequences. They also emphasize the differences between gene regulation in MEL cells, transgenic mice, and retroviral gene transfer vectors. For this form of globin gene therapy to succeed, the proximal regulatory elements of the human gamma-globin gene may have to be replaced with different regulatory elements that allow the expression of the gamma-globin coding sequences in adult red cells in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1079-9796
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Academic Press.
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
613-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
In vivo silencing of the human gamma-globin gene in murine erythroid cells following retroviral transduction.
pubmed:affiliation
Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't