Titre
Evidence that the mouse 3' kappa light chain enhancer confers position-independent transgene expression in T- and B-lineage cells
Type
article
Institution
Externe
Périodique
Auteur(s)
Xu, L.
Auteure/Auteur
Tsuji, K.
Auteure/Auteur
Mostowski, H.
Auteure/Auteur
Candotti, F.
Auteure/Auteur
Rosenberg, A.
Auteure/Auteur
Liens vers les personnes
ISSN
1043-0342
Statut éditorial
Publié
Date de publication
2003
Volume
14
Numéro
18
Première page
1753
Dernière page/numéro d’article
64
Langue
anglais
Notes
Xu, Lai
Tsuji, Kazuhide
Mostowski, Howard
Candotti, Fabio
Rosenberg, Amy
eng
Hum Gene Ther. 2003 Dec 10;14(18):1753-64.
Tsuji, Kazuhide
Mostowski, Howard
Candotti, Fabio
Rosenberg, Amy
eng
Hum Gene Ther. 2003 Dec 10;14(18):1753-64.
Résumé
One of the major obstacles for successful application of murine leukemia virus (MLV) vectors to genetic therapy of lymphocyte disorders is low levels of transgene expression or the eventual loss of expression. To overcome this problem, an improved retroviral vector was constructed utilizing the myeloproliferative sarcoma virus (MPSV) long terminal repeat (LTR), which provided a significantly higher level of transgene expression in human lymphoid cells than did MLV vectors. Nevertheless, transgene expression remained low in a large percentage of transduced cells. To address whether lymphocyte enhancer elements might improve transgene expression mediated by retroviral vectors in lymphocytes, we cloned the mouse immunoglobulin 3' kappa light chain enhancer gene (mE3') into the MPSV vector. We found that the mE3' conferred a higher, more uniform and sustained level of expression in transduced T- and B-cell lines, and in primary T cells, than did the control vector lacking this element. Integration sites were diverse and a single copy of the proviral genome was present in all examined transduced cells. The mE3' failed to enhance transgene expression in most nonlymphoid cells, indicating it is relatively lineage-specific. Taken together, these results provide strong evidence that the mE3' functions as a locus control region (LCR) in conferring enhanced integration-site-independent expression of a retroviral transgene.
PID Serval
serval:BIB_6A912066BB62
PMID
Date de création
2017-11-01T09:29:36.017Z
Date de création dans IRIS
2025-05-20T21:54:41Z