Document Detail


Delivery of genes to hematopoietic stem cells.
MedLine Citation:
PMID:  14970614     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bone marrow hematopoiesis is maintained by hematopoietic stem cells (HSC). Because of their unique features to self-renew and differentiate along all lineages of hematopoietic cells, even a single HSC can completely reconstitute bone marrow hematopoiesis of irradiated recipients (2). Therefore, HSCs are considered to be the ideal target cell population in gene-therapy fields for genetic disorders that are susceptible to bone marrow transplantation (3). However, because most HSCs are quiescent, it is difficult to transduce them using retroviral vectors (4). Furthermore, retroviral vectors, especially Moloney murine leukemia virus (MMLV)-based retroviral vectors that have been commonly used in gene-therapy clinical trials, are very susceptible to de novo methylation in immature cells such as embryonic stem (ES) cells, embryonal carcinoma cells (EC), and HSCs, resulting in shut off/silencing of the transgene expression in vivo (5). This is another obstacle for successful gene delivery into HSCs.
Authors:
Masafumi Onodera
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Methods in molecular biology (Clifton, N.J.)     Volume:  246     ISSN:  1064-3745     ISO Abbreviation:  Methods Mol. Biol.     Publication Date:  2004  
Date Detail:
Created Date:  2004-02-18     Completed Date:  2004-03-19     Revised Date:  2006-04-21    
Medline Journal Info:
Nlm Unique ID:  9214969     Medline TA:  Methods Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  527-39     Citation Subset:  IM    
Affiliation:
Department of Hematology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Gene Transfer Techniques*
Genetic Vectors
Hematopoietic Stem Cells / metabolism*
Mice
Retroviridae / genetics
Transduction, Genetic
Viral Structural Proteins / genetics
Chemical
Reg. No./Substance:
0/Viral Structural Proteins

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