Integration and exchange of split dCas9 domains for transcriptional controls in mammalian cells.
Nat Commun
; 7: 13056, 2016 10 03.
Article
em En
| MEDLINE
| ID: mdl-27694915
ABSTRACT
Programmable and precise regulation of dCas9 functions in response to multiple molecular signals by using synthetic gene circuits will expand the application of the CRISPR-Cas technology. However, the application of CRISPR-Cas therapeutic circuits is still challenging due to the restrictive cargo size of existing viral delivery vehicles. Here, we construct logic AND circuits by integrating multiple split dCas9 domains, which is useful to reduce the size of synthetic circuits. In addition, we engineer sensory switches by exchanging split dCas9 domains, allowing differential regulations on one gene, or activating two different genes in response to cell-type specific microRNAs. Therefore, we provide a valuable split-dCas9 toolkit to engineer complex transcription controls, which may inspire new biomedical applications.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Regulação da Expressão Gênica
/
Sistemas CRISPR-Cas
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article