Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia
A circuit level understanding of immune cells and hematological cancers has been severely impeded by a lack of techniques that enable intracellular perturbation without significantly altering cell viability and function. Here, we demonstrate that vertical silicon nanowires (NWs) enable gene-specific...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2013
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| Online Access: | http://hdl.handle.net/1721.1/82108 https://orcid.org/0000-0001-8567-2049 |
| _version_ | 1826192634921615360 |
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| author | Shalek, Alex K. Gaublomme, Jellert T. Wang, Lili Yosef, Nir Chevrier, Nicolas Andersen, Mette S. Robinson, Jacob T. Pochet, Nathalie Neuberg, Donna S. Gertner, Rona S. Amit, Ido Brown, Jennifer R. Hacohen, Nir Regev, Aviv Wu, Catherine J. Park, Hongkun |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Shalek, Alex K. Gaublomme, Jellert T. Wang, Lili Yosef, Nir Chevrier, Nicolas Andersen, Mette S. Robinson, Jacob T. Pochet, Nathalie Neuberg, Donna S. Gertner, Rona S. Amit, Ido Brown, Jennifer R. Hacohen, Nir Regev, Aviv Wu, Catherine J. Park, Hongkun |
| author_sort | Shalek, Alex K. |
| collection | MIT |
| description | A circuit level understanding of immune cells and hematological cancers has been severely impeded by a lack of techniques that enable intracellular perturbation without significantly altering cell viability and function. Here, we demonstrate that vertical silicon nanowires (NWs) enable gene-specific manipulation of diverse murine and human immune cells with negligible toxicity. To illustrate the power of the technique, we then apply NW-mediated gene silencing to investigate the role of the Wnt signaling pathway in chronic lymphocytic leukemia (CLL). Remarkably, CLL-B cells from different patients exhibit tremendous heterogeneity in their response to the knockdown of a single gene, LEF1. This functional heterogeneity defines three distinct patient groups not discernible by conventional CLL cytogenetic markers and provides a prognostic indicator for patients’ time to first therapy. Analyses of gene expression signatures associated with these functional patient subgroups reveal unique insights into the underlying molecular basis for disease heterogeneity. Overall, our findings suggest a functional classification that can potentially guide the selection of patient-specific therapies in CLL and highlight the opportunities for nanotechnology to drive biological inquiry. |
| first_indexed | 2024-09-23T09:25:12Z |
| format | Article |
| id | mit-1721.1/82108 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:25:12Z |
| publishDate | 2013 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/821082022-09-26T11:24:02Z Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia Shalek, Alex K. Gaublomme, Jellert T. Wang, Lili Yosef, Nir Chevrier, Nicolas Andersen, Mette S. Robinson, Jacob T. Pochet, Nathalie Neuberg, Donna S. Gertner, Rona S. Amit, Ido Brown, Jennifer R. Hacohen, Nir Regev, Aviv Wu, Catherine J. Park, Hongkun Massachusetts Institute of Technology. Department of Biology Regev, Aviv A circuit level understanding of immune cells and hematological cancers has been severely impeded by a lack of techniques that enable intracellular perturbation without significantly altering cell viability and function. Here, we demonstrate that vertical silicon nanowires (NWs) enable gene-specific manipulation of diverse murine and human immune cells with negligible toxicity. To illustrate the power of the technique, we then apply NW-mediated gene silencing to investigate the role of the Wnt signaling pathway in chronic lymphocytic leukemia (CLL). Remarkably, CLL-B cells from different patients exhibit tremendous heterogeneity in their response to the knockdown of a single gene, LEF1. This functional heterogeneity defines three distinct patient groups not discernible by conventional CLL cytogenetic markers and provides a prognostic indicator for patients’ time to first therapy. Analyses of gene expression signatures associated with these functional patient subgroups reveal unique insights into the underlying molecular basis for disease heterogeneity. Overall, our findings suggest a functional classification that can potentially guide the selection of patient-specific therapies in CLL and highlight the opportunities for nanotechnology to drive biological inquiry. National Institutes of Health (U.S.). Pioneer Award National Institutes of Health (U.S.) (CEGS Award 1P50HG006193-01) Howard Hughes Medical Institute Merkin Family Foundation for Stem Cell Research 2013-11-13T17:16:27Z 2013-11-13T17:16:27Z 2012-11 2012-11 Article http://purl.org/eprint/type/JournalArticle 1530-6984 1530-6992 http://hdl.handle.net/1721.1/82108 Shalek, Alex K., Jellert T. Gaublomme, Lili Wang, Nir Yosef, Nicolas Chevrier, Mette S. Andersen, Jacob T. Robinson, et al. “Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia.” Nano Letters 12, no. 12 (December 12, 2012): 6498-6504. © 2012 American Chemical Society https://orcid.org/0000-0001-8567-2049 en_US http://dx.doi.org/10.1021/nl3042917 Nano Letters Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Shalek, Alex K. Gaublomme, Jellert T. Wang, Lili Yosef, Nir Chevrier, Nicolas Andersen, Mette S. Robinson, Jacob T. Pochet, Nathalie Neuberg, Donna S. Gertner, Rona S. Amit, Ido Brown, Jennifer R. Hacohen, Nir Regev, Aviv Wu, Catherine J. Park, Hongkun Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia |
| title | Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia |
| title_full | Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia |
| title_fullStr | Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia |
| title_full_unstemmed | Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia |
| title_short | Nanowire-Mediated Delivery Enables Functional Interrogation of Primary Immune Cells: Application to the Analysis of Chronic Lymphocytic Leukemia |
| title_sort | nanowire mediated delivery enables functional interrogation of primary immune cells application to the analysis of chronic lymphocytic leukemia |
| url | http://hdl.handle.net/1721.1/82108 https://orcid.org/0000-0001-8567-2049 |
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