Document Detail


Efficient retrovirus-mediated transfer of the multidrug resistance 1 gene into autologous human long-term repopulating hematopoietic stem cells.
MedLine Citation:
PMID:  10835681     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pre-clinical studies indicate that efficient retrovirus-mediated gene transfer into hematopoietic stem cells and progenitor cells can be achieved by co-localizing retroviral particles and target cells on specific adhesion domains of fibronectin. In this pilot study, we used this technique to transfer the human multidrug resistance 1 gene into stem and progenitor cells of patients with germ cell tumors undergoing autologous transplantation. There was efficient gene transfer into stem and progenitor cells in the presence of recombinant fibronectin fragment CH-296. The infusion of these cells was associated with no harmful effects and led to prompt hematopoietic recovery. There was in vivo vector expression, but it may have been limited by the high rate of aberrant splicing of the multidrug resistance 1 gene in the vector. Gene marking has persisted more than a year at levels higher than previously reported in humans.
Authors:
R Abonour; D A Williams; L Einhorn; K M Hall; J Chen; J Coffman; C M Traycoff; A Bank; I Kato; M Ward; S D Williams; R Hromas; M J Robertson; F O Smith; D Woo; B Mills; E F Srour; K Cornetta
Publication Detail:
Type:  Clinical Trial; Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nature medicine     Volume:  6     ISSN:  1078-8956     ISO Abbreviation:  Nat. Med.     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-07-24     Completed Date:  2000-07-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9502015     Medline TA:  Nat Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  652-8     Citation Subset:  IM    
Affiliation:
Department of Medicine, Howard Hughes Medical Institute, Indiana University School of Medicine, 1044 W. Walnut, Rm. 402, Indianapolis, IN 46202, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Antigens, CD34
Fibronectins / genetics*
Follow-Up Studies
Gene Therapy / methods
Gene Transfer Techniques*
Genes, MDR*
Genetic Vectors*
Germinoma / therapy*
Hematopoietic Stem Cell Transplantation*
Hematopoietic Stem Cells / cytology*
Humans
Middle Aged
Pilot Projects
Retroviridae*
Time Factors
Treatment Outcome
Grant Support
ID/Acronym/Agency:
CA11148/CA/NCI NIH HHS; M01 RR00750/RR/NCRR NIH HHS; U42 RR/1148/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD34; 0/Fibronectins
Comments/Corrections
Comment In:
Nat Med. 2000 Jun;6(6):624-6   [PMID:  10835670 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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