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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Delaney, Alexandra Chen, Clark C. Anufreichik, Veronika Zanetti, Maurizio Chiu, Kevin T. Akers, Johnny C. Almanza, Gonzalo Rodvold, Jeffrey J. |
| Description | Author Affiliation: Almanza G ( Laboratory of Immunology, Department of Medicine and Moores Cancer Center, and Center for Theoretical and Applied Neuro-Oncology, Division of Neurosurgery and Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093-0815.); |
| Abstract | Evolutionarily conserved short (20-30 nucleotides) noncoding RNAs (microRNAs) are powerful regulators of gene expression in a variety of physiological and pathological processes. As such, means to efficiently modulate microRNA function constitute an important therapeutic opportunity. Here we demonstrate that primary B lymphocytes can be genetically programmed with nonviral plasmid DNA for the biogenesis and delivery of antisense sequences (anti-microRNA) against microRNA-150 (miR-150). Within 18 h of transfection with an anti-miR-150 construct, primary B lymphocytes secrete â ¼3,000 copies of anti-miR-150 molecules per cell. Anti-miR-150 molecules released by B lymphocytes were internalized by CD8 T lymphocytes during cross-priming in vitro and in vivo, resulting in marked down-regulation of endogenous miR-150. However, such internalization was not observed in the absence of cross-priming. These results suggest that shuttling anti-miR-150 molecules from B lymphocytes to T cells requires the activation of receiver T cells via the antigen receptor. Finally, anti-miR-150 synthesized in B cells were secreted both as free and extracellular vesicle-associated fractions, but only extracellular vesicle-associated anti-miR-150 were apparently taken up by CD8 T cells. Collectively, these data indicate that primary B lymphocytes represent an efficient platform for the synthesis and delivery of short, noncoding RNA, paving the way for an approach to immunogenomic therapies. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 50 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | B-Lymphocytes Metabolism Gene Expression Regulation Genetics Gene Targeting Immunotherapy MicroRNAs RNA, Small Untranslated Biosynthesis Animals Antibodies Immunology Cross-Priming Flow Cytometry Mice Mice, Inbred C57BL Microscopy, Fluorescence Oligonucleotides Plasmids Real-Time Polymerase Chain Reaction Transfection Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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