Multimode drug inducible CRISPR/Cas9 devices for transcriptional activation and genome editing.
Nucleic Acids Res
; 46(5): e25, 2018 03 16.
Article
em En
| MEDLINE
| ID: mdl-29237052
ABSTRACT
Precise investigation and manipulation of dynamic biological processes often requires molecular modulation in a controlled inducible manner. The clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) has emerged as a versatile tool for targeted gene editing and transcriptional programming. Here, we designed and vigorously optimized a series of Hybrid drug Inducible CRISPR/Cas9 Technologies (HIT) for transcriptional activation by grafting a mutated human estrogen receptor (ERT2) to multiple CRISPR/Cas9 systems, which renders them 4-hydroxytamoxifen (4-OHT) inducible for the access of genome. Further, extra functionality of simultaneous genome editing was achieved with one device we named HIT2. Optimized terminal devices herein delivered advantageous performances in comparison with several existing designs. They exerted selective, titratable, rapid and reversible response to drug induction. In addition, these designs were successfully adapted to an orthogonal Cas9. HIT systems developed in this study can be applied for controlled modulation of potentially any genomic loci in multiple modes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tamoxifeno
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Ativação Transcricional
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Receptor beta de Estrogênio
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Sistemas CRISPR-Cas
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Edição de Genes
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China