Highly efficient Cas9-mediated transcriptional programming
The RNA-guided nuclease Cas9 can be reengineered as a programmable transcription factor. However, modest levels of gene activation have limited potential applications. We describe an improved transcriptional regulator obtained through the rational design of a tripartite activator, VP64-p65-Rta (VPR)...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2015
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| Online Access: | http://hdl.handle.net/1721.1/99529 https://orcid.org/0000-0003-0396-2443 https://orcid.org/0000-0003-1736-0937 https://orcid.org/0000-0002-5560-8246 |
| _version_ | 1810986134041264128 |
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| author | Chavez, Alejandro Scheiman, Jonathan Tuttle, Marcelle Lin, Shuailiang Kiani, Samira Ter-Ovanesyan, Dmitry Davidsohn, Noah Perrimon, Norbert Weiss, Ron Aach, John Vora, Suhani Deepak Pruitt, Benjamin W. Iyer, Eswar P. R. Guzman, Christopher D. Wiegand, Daniel J. Braff, Jonathan L. Housden, Benjamin E. Collins, James J. Church, George M. |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Chavez, Alejandro Scheiman, Jonathan Tuttle, Marcelle Lin, Shuailiang Kiani, Samira Ter-Ovanesyan, Dmitry Davidsohn, Noah Perrimon, Norbert Weiss, Ron Aach, John Vora, Suhani Deepak Pruitt, Benjamin W. Iyer, Eswar P. R. Guzman, Christopher D. Wiegand, Daniel J. Braff, Jonathan L. Housden, Benjamin E. Collins, James J. Church, George M. |
| author_sort | Chavez, Alejandro |
| collection | MIT |
| description | The RNA-guided nuclease Cas9 can be reengineered as a programmable transcription factor. However, modest levels of gene activation have limited potential applications. We describe an improved transcriptional regulator obtained through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9. We demonstrate its utility in activating endogenous coding and noncoding genes, targeting several genes simultaneously and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs). |
| first_indexed | 2024-09-23T11:29:23Z |
| format | Article |
| id | mit-1721.1/99529 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:29:23Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/995292024-03-20T19:51:07Z Highly efficient Cas9-mediated transcriptional programming Chavez, Alejandro Scheiman, Jonathan Tuttle, Marcelle Lin, Shuailiang Kiani, Samira Ter-Ovanesyan, Dmitry Davidsohn, Noah Perrimon, Norbert Weiss, Ron Aach, John Vora, Suhani Deepak Pruitt, Benjamin W. Iyer, Eswar P. R. Guzman, Christopher D. Wiegand, Daniel J. Braff, Jonathan L. Housden, Benjamin E. Collins, James J. Church, George M. Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology. Synthetic Biology Center Vora, Suhani Deepak Kiani, Samira Weiss, Ron Collins, James J. The RNA-guided nuclease Cas9 can be reengineered as a programmable transcription factor. However, modest levels of gene activation have limited potential applications. We describe an improved transcriptional regulator obtained through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9. We demonstrate its utility in activating endogenous coding and noncoding genes, targeting several genes simultaneously and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs). National Human Genome Research Institute (U.S.) (Grant P50 HG005550) United States. Dept. of Energy (Grant DE-FG02-02ER63445) Wyss Institute for Biologically Inspired Engineering National Science Foundation (U.S.). Graduate Research Fellowship Massachusetts Institute of Technology. Department of Biological Engineering Harvard Medical School. Department of Genetics 2015-10-30T17:46:23Z 2015-10-30T17:46:23Z 2015-03 2014-12 Article http://purl.org/eprint/type/JournalArticle 1548-7091 1548-7105 http://hdl.handle.net/1721.1/99529 Chavez, Alejandro, Jonathan Scheiman, Suhani Vora, Benjamin W Pruitt, Marcelle Tuttle, Eswar P R Iyer, Shuailiang Lin, et al. “Highly Efficient Cas9-Mediated Transcriptional Programming.” Nat Meth 12, no. 4 (March 2, 2015): 326–328. https://orcid.org/0000-0003-0396-2443 https://orcid.org/0000-0003-1736-0937 https://orcid.org/0000-0002-5560-8246 en_US http://dx.doi.org/10.1038/nmeth.3312 Nature Methods 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 Nature Publishing Group PMC |
| spellingShingle | Chavez, Alejandro Scheiman, Jonathan Tuttle, Marcelle Lin, Shuailiang Kiani, Samira Ter-Ovanesyan, Dmitry Davidsohn, Noah Perrimon, Norbert Weiss, Ron Aach, John Vora, Suhani Deepak Pruitt, Benjamin W. Iyer, Eswar P. R. Guzman, Christopher D. Wiegand, Daniel J. Braff, Jonathan L. Housden, Benjamin E. Collins, James J. Church, George M. Highly efficient Cas9-mediated transcriptional programming |
| title | Highly efficient Cas9-mediated transcriptional programming |
| title_full | Highly efficient Cas9-mediated transcriptional programming |
| title_fullStr | Highly efficient Cas9-mediated transcriptional programming |
| title_full_unstemmed | Highly efficient Cas9-mediated transcriptional programming |
| title_short | Highly efficient Cas9-mediated transcriptional programming |
| title_sort | highly efficient cas9 mediated transcriptional programming |
| url | http://hdl.handle.net/1721.1/99529 https://orcid.org/0000-0003-0396-2443 https://orcid.org/0000-0003-1736-0937 https://orcid.org/0000-0002-5560-8246 |
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