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Systemic in vivo lentiviral delivery of miR-15a/16 reduces malignancy in the NZB de novo mouse model of chronic lymphocytic leukemia

Genes & Immunity volume 13, pages 109–119 (2012)Cite this article

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.

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Acknowledgements

We would like to thank the UMDNJ-NJMS Flow Cytometry Core. This research was funded in part by NIH R01CA129826 (ER) and the NJ Commission on Cancer Research predoctoral fellowship 09-1255-CCR-E0 (ES).

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  1. S Kasar and E Salerno: These authors are co-first authors.

Authors and Affiliations

  1. Department of Pathology and Lab Medicine, University of Medicine and Dentistry/New Jersey Medical School, Newark, NJ, USA

    S Kasar, E Salerno, Y Yuan, C Underbayev, D Vollenweider, M F Laurindo, H Fernandes, F Mazzella & E Raveche

  2. Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore Sanità, Rome, Italy

    D Bonci & A Addario

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Correspondence to E Raveche.

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Kasar, S., Salerno, E., Yuan, Y. et al. Systemic in vivo lentiviral delivery of miR-15a/16 reduces malignancy in the NZB de novo mouse model of chronic lymphocytic leukemia. Genes Immun 13, 109–119 (2012). https://doi.org/10.1038/gene.2011.58

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