DNA sense-and-respond protein modules for mammalian cells
We generated synthetic protein components that can detect specific DNA sequences and subsequently trigger a desired intracellular response. These modular sensors exploit the programmability of zinc-finger DNA recognition to drive the intein-mediated splicing of an artificial trans-activator that sig...
| Main Authors: | , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Nature Publishing Group
2017
|
| Online Access: | http://hdl.handle.net/1721.1/108502 https://orcid.org/0000-0003-4873-3222 https://orcid.org/0000-0002-5560-8246 |
| _version_ | 1826198191723249664 |
|---|---|
| author | Slomovic, Shimyn Collins, James J. |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Slomovic, Shimyn Collins, James J. |
| author_sort | Slomovic, Shimyn |
| collection | MIT |
| description | We generated synthetic protein components that can detect specific DNA sequences and subsequently trigger a desired intracellular response. These modular sensors exploit the programmability of zinc-finger DNA recognition to drive the intein-mediated splicing of an artificial trans-activator that signals to a genetic circuit containing a given reporter or response gene. We used the sensors to mediate sequence recognition−induced apoptosis as well as to detect and report a viral infection. This work establishes a synthetic biology framework for endowing mammalian cells with sentinel capabilities, which provides a programmable means to cull infected cells. It may also be used to identify positively transduced or transfected cells, isolate recipients of intentional genomic edits and increase the repertoire of inducible parts in synthetic biology. |
| first_indexed | 2024-09-23T11:00:42Z |
| format | Article |
| id | mit-1721.1/108502 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:00:42Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1085022024-03-20T19:42:05Z DNA sense-and-respond protein modules for mammalian cells Slomovic, Shimyn Collins, James J. Massachusetts Institute of Technology. Institute for Medical Engineering & Science Collins, James Slomovic, Shimyn Collins, James J. We generated synthetic protein components that can detect specific DNA sequences and subsequently trigger a desired intracellular response. These modular sensors exploit the programmability of zinc-finger DNA recognition to drive the intein-mediated splicing of an artificial trans-activator that signals to a genetic circuit containing a given reporter or response gene. We used the sensors to mediate sequence recognition−induced apoptosis as well as to detect and report a viral infection. This work establishes a synthetic biology framework for endowing mammalian cells with sentinel capabilities, which provides a programmable means to cull infected cells. It may also be used to identify positively transduced or transfected cells, isolate recipients of intentional genomic edits and increase the repertoire of inducible parts in synthetic biology. United States. Defense Advanced Research Projects Agency (DARPA-BAA-11-23) Defense Threat Reduction Agency (DTRA) (HDTRA1-14-1-0006) United States. Air Force Office of Scientific Research (FA9550-14-1-0060) 2017-04-28T18:28:28Z 2017-04-28T18:28:28Z 2015-09 2015-06 Article http://purl.org/eprint/type/JournalArticle 1548-7091 1548-7105 http://hdl.handle.net/1721.1/108502 Slomovic, Shimyn and Collins, James J. “DNA Sense-and-Respond Protein Modules for Mammalian Cells.” Nature Methods 12, no. 11 (September 21, 2015): 1085–1090. © 2015 Macmillan Publishers Limited, part of Springer Nature https://orcid.org/0000-0003-4873-3222 https://orcid.org/0000-0002-5560-8246 en_US http://dx.doi.org/10.1038/nmeth.3585 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 Prof. Collins via Howard Silver |
| spellingShingle | Slomovic, Shimyn Collins, James J. DNA sense-and-respond protein modules for mammalian cells |
| title | DNA sense-and-respond protein modules for mammalian cells |
| title_full | DNA sense-and-respond protein modules for mammalian cells |
| title_fullStr | DNA sense-and-respond protein modules for mammalian cells |
| title_full_unstemmed | DNA sense-and-respond protein modules for mammalian cells |
| title_short | DNA sense-and-respond protein modules for mammalian cells |
| title_sort | dna sense and respond protein modules for mammalian cells |
| url | http://hdl.handle.net/1721.1/108502 https://orcid.org/0000-0003-4873-3222 https://orcid.org/0000-0002-5560-8246 |
| work_keys_str_mv | AT slomovicshimyn dnasenseandrespondproteinmodulesformammaliancells AT collinsjamesj dnasenseandrespondproteinmodulesformammaliancells |