title: Systemic in vivo lentiviral delivery of miR-15a/16 reduces malignancy in the NZB de novo mouse model of chronic lymphocytic leukemia.
abstract: 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.
authors: Department of Pathology and Lab Medicine, University of Medicine and Dentistry/New Jersey Medical School, Newark, NJ 07103, USA.
authors: S
authors: S
authors: Kasar
authors: E
authors: E
authors: Salerno
authors: Y
authors: Y
authors: Yuan
authors: C
authors: C
authors: Underbayev
authors: D
authors: D
authors: Vollenweider
authors: M F
authors: MF
authors: Laurindo
authors: H
authors: H
authors: Fernandes
authors: D
authors: D
authors: Bonci
authors: A
authors: A
authors: Addario
authors: F
authors: F
authors: Mazzella
authors: E
authors: E
authors: Raveche
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015316:Genetic Therapy; D016086:Lentivirus / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*
chemical_list: D035683:MicroRNAs