Article (Scientific journals)
Development of B-lineage predominant lentiviral vectors for use in genetic therapies for B cell disorders
Sather, B. D.; Ryu, B. Y.; Stirling, B. V. et al.
2011In Molecular Therapy, 19 (3), p. 515-25
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Abstract :
[en] Sustained, targeted, high-level transgene expression in primary B lymphocytes may be useful for gene therapy in B cell disorders. We developed several candidate B-lineage predominant self-inactivating lentiviral vectors (LC) containing alternative enhancer/promoter elements including : the immunoglobulin β (Igβ) promoter combined with the immunoglobulin µ enhancer (EµB29); and the endogenous BTK promoter with or without Eµ (EµBtkp or Btkp). LV-driven enhanced green fluorescent protein (eGFP) reporter expression was evaluated in cell lines and primary cells derived from human or murine hematopoietic stem cells (HSC). In murine primary cells, eµB29 and EµBtkp LV-mediated high-level expression in immature and mature B cells compared with all other lineages. Expression increased with B cell maturation and was maintained in peripheral subsets. Expression in T and myeloid cells was much lower in percentage and intensity. Similarly, both EµB29 and EµBtkp LV exhibited high-level activity in human primary B cells. In contrast to EµB29, Btkp and EµBtkp LV also exhibited modest actiity in myeloid cells, consistent with the expression profile of endogenous Bruton's tyrosine kinase (Btk). Notably, EµB29 end EµBtkp activity was superior in all expression models to an alternative, B-lineage targeted vector containing the EµS.CD19 enhancer/promoter. In summary, EµB29 and EµBtkp LV comprise efficient delivery platforms for gene expression in B-lineage cells.
Disciplines :
Hematology
Author, co-author :
Sather, B. D.
Ryu, B. Y.
Stirling, B. V.
Garibov, M.
Kerns, H. M.
Humblet, Stéphanie ;  Université de Liège - ULiège > GIGA-R : Hématologie
Astrakhan, A.
Rawlings, D. J.
Language :
English
Title :
Development of B-lineage predominant lentiviral vectors for use in genetic therapies for B cell disorders
Publication date :
2011
Journal title :
Molecular Therapy
ISSN :
1525-0016
eISSN :
1525-0024
Publisher :
Nature Publishing Group, San Diego, United States - California
Volume :
19
Issue :
3
Pages :
515-25
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 27 January 2012

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