Systemic in vivo lentiviral delivery of miR-15a/16 reduces malignancy in the NZB de novo mouse model of chronic lymphocytic leukemia.
Détails
Télécharger: 21881595_BIB_9CB146AFE82F.pdf (1129.03 [Ko])
Etat: Public
Version: Author's accepted manuscript
Licence: Non spécifiée
Etat: Public
Version: Author's accepted manuscript
Licence: Non spécifiée
ID Serval
serval:BIB_9CB146AFE82F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Systemic in vivo lentiviral delivery of miR-15a/16 reduces malignancy in the NZB de novo mouse model of chronic lymphocytic leukemia.
Périodique
Genes and Immunity
ISSN
1476-5470 (Electronic)
ISSN-L
1466-4879
Statut éditorial
Publié
Date de publication
2012
Volume
13
Numéro
2
Pages
109-119
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
Similar to human chronic lymphocytic leukemia (CLL), the de novo New Zealand Black (NZB) mouse model has a genetically determined age-associated increase in malignant B-1 clones and decreased expression of microRNAs miR-15a and miR-16 in B-1 cells. In the present study, lentiviral vectors were employed in vivo to restore miR-15a/16, and both the short-term single injection and long-term multiple injection effects of this delivery were observed in NZB. Control lentivirus without the mir-15a/16 sequence was used for comparison. We found that in vivo lentiviral delivery of mir-15a/16 increased miR-15a/16 expression in cells that were transduced (detected by GFP expression) and in sera when compared with control lentivirus treatment. More importantly, mice treated with the miR-expressing lentivirus had decreased disease. The lentivirus had little systemic toxicity while preferentially targeting B-1 cells. Short-term effects on B-1 cells were direct effects, and only malignant B-1 cells transduced with miR-15a/16 lentivirus had decreased viability. In contrast, long-term studies suggested both direct and indirect effects resulting from miR-15a/16 lentivirus treatment. A decrease in B-1 cells was found in both the transduced and non-transduced populations. Our data support the potential use of systemic lentiviral delivery of miR-15a/16 to ameliorate disease manifestations of CLL.
Mots-clé
Animals, Disease Models, Animal, Genetic Therapy, Lentivirus/genetics, Leukemia, Lymphocytic, Chronic, B-Cell/genetics, Leukemia, Lymphocytic, Chronic, B-Cell/pathology, Mice, MicroRNAs/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/11/2011 13:23
Dernière modification de la notice
20/08/2019 16:03