An enhanced CRISPR repressor for targeted mammalian gene regulation
The RNA-guided endonuclease Cas9 can be converted into a programmable transcriptional repressor, but inefficiencies in target-gene silencing have limited its utility. Here we describe an improved Cas9 repressor based on the C-terminal fusion of a rationally designed bipartite repressor domain, KRAB–...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2018
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| _version_ | 1826274105505087488 |
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| author | Yeo, NC Chavez, A Lance-Byrne, A Chan, Y Menn, D Milanova, D Kuo, C-C Guo, X Sharma, S Tung, A Cecchi, RJ Tuttle, M Pradhan, S Lim, ET Davidsohn, N Ebrahimkhani, MR Collins, JJ Lewis, NE Kiani, S Church, GM |
| author_facet | Yeo, NC Chavez, A Lance-Byrne, A Chan, Y Menn, D Milanova, D Kuo, C-C Guo, X Sharma, S Tung, A Cecchi, RJ Tuttle, M Pradhan, S Lim, ET Davidsohn, N Ebrahimkhani, MR Collins, JJ Lewis, NE Kiani, S Church, GM |
| author_sort | Yeo, NC |
| collection | OXFORD |
| description | The RNA-guided endonuclease Cas9 can be converted into a programmable transcriptional repressor, but inefficiencies in target-gene silencing have limited its utility. Here we describe an improved Cas9 repressor based on the C-terminal fusion of a rationally designed bipartite repressor domain, KRAB–MeCP2, to nuclease-dead Cas9. We demonstrate the system’s superiority in silencing coding and noncoding genes, simultaneously repressing a series of target genes, improving the results of single and dual guide RNA library screens, and enabling new architectures of synthetic genetic circuits. |
| first_indexed | 2024-03-06T22:38:23Z |
| format | Journal article |
| id | oxford-uuid:5ab3e90b-a9ed-4600-9a0d-6ba73854fcee |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:38:23Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:5ab3e90b-a9ed-4600-9a0d-6ba73854fcee2022-03-26T17:17:34ZAn enhanced CRISPR repressor for targeted mammalian gene regulationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5ab3e90b-a9ed-4600-9a0d-6ba73854fceeEnglishSymplectic ElementsSpringer Nature2018Yeo, NCChavez, ALance-Byrne, AChan, YMenn, DMilanova, DKuo, C-CGuo, XSharma, STung, ACecchi, RJTuttle, MPradhan, SLim, ETDavidsohn, NEbrahimkhani, MRCollins, JJLewis, NEKiani, SChurch, GMThe RNA-guided endonuclease Cas9 can be converted into a programmable transcriptional repressor, but inefficiencies in target-gene silencing have limited its utility. Here we describe an improved Cas9 repressor based on the C-terminal fusion of a rationally designed bipartite repressor domain, KRAB–MeCP2, to nuclease-dead Cas9. We demonstrate the system’s superiority in silencing coding and noncoding genes, simultaneously repressing a series of target genes, improving the results of single and dual guide RNA library screens, and enabling new architectures of synthetic genetic circuits. |
| spellingShingle | Yeo, NC Chavez, A Lance-Byrne, A Chan, Y Menn, D Milanova, D Kuo, C-C Guo, X Sharma, S Tung, A Cecchi, RJ Tuttle, M Pradhan, S Lim, ET Davidsohn, N Ebrahimkhani, MR Collins, JJ Lewis, NE Kiani, S Church, GM An enhanced CRISPR repressor for targeted mammalian gene regulation |
| title | An enhanced CRISPR repressor for targeted mammalian gene regulation |
| title_full | An enhanced CRISPR repressor for targeted mammalian gene regulation |
| title_fullStr | An enhanced CRISPR repressor for targeted mammalian gene regulation |
| title_full_unstemmed | An enhanced CRISPR repressor for targeted mammalian gene regulation |
| title_short | An enhanced CRISPR repressor for targeted mammalian gene regulation |
| title_sort | enhanced crispr repressor for targeted mammalian gene regulation |
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