<p>SUPPLEMENTAL MATERIAL</p><p>Supplementary Figure 1. Analysis of miR-15a/16 effects in the PWC. NZB mice</p><p>(9mo) were injected with empty (GFP-Lentivirus, left) or mir-15a/16-lentivirus </p><p>(miR Lentivirus, right) and analyzed (8 days post) for GFP expression in B-1 cells</p><p>(CD5 dull, B220+), B-2 cells (CD5-, B220+) or T cells (CD5+, B220-). The percent GFP+ cells as a percent of the total in that population is indicated in the upper right corner of the histograms. GFP+ cells were found in the B cell population indicating that B cells preferentially were transduced. Supplementary Figure 2. Percent change in B-1 cells following short-term lentivirus treatment. NZB mice 9-12 mo were either uninjected or injected with mir-15a/16 lentivirus or control lentivirus and spleens analyzed 8 days post treatment. Columns are Mean % change ± SD. The % Change was calculated as </p><p>% B-1 in lenti - % B-1 untreated %B-1 untreated X 100</p><p>* indicates statistical significance, student’s t-test, p<0.05, n=6 control lenti, n=7 mir-lenti, n=3 untreated. Supplementary Figure 3. Effect of in vivo miR-15a/16 restoration in NZB mice on aneuploidy. NZB mice were injected with either a control lentiviral vector expressing GFP (control) only or a lentiviral vector expressing both GFP and the wild-type mir-15a/16-1 sequence (miR-15a/16). NZB were evaluated for short- term effects (8-9 days) and long-term effects (28-29 days) of miR-15a/16 restoration post-injection. A, Representative analysis of DNA content (by computer modeling) of NZB injected with control vector and miR-15a/16 lentiviral vector, (short-term = spleen, long-term = PWC). The first tallest peaks represent diploid G1 with the smaller peak to the right representing aneuploid G1. B, </p><p>Percentage of cells with aneuploidy in PWC, spleen, and PB from NZB injected with control or miR-15a/16-expressing lentivirus, left = short-term, right = long- term of PWC, spleen, and PB of NZB treated with control or miR-15a/16- expressing lentivirus. Black columns = control-lenti and white = miR-15a/16-lenti. Error bars represent SEM (short-term: control n = 5, miR-15a/16 n = 8; long-term: control n = 4, miR-15a/16 n = 4).</p><p>The percent of aneuploidy did not differ between NZB mice injected with either the control or miR-15a/16 lentiviruses in any tissue in the short-term study. </p><p>In the long-term study, which involved two injections, there was a trend in all tissues analyzed for a decrease in aneuploid cells in the long-term NZB injected with mir-15a/16-lentivirus when compared to NZB treated with control-lentivirus. </p>