Development of an ObLiGaRe Doxycycline Inducible Cas9 system for pre-clinical cancer drug discovery.
Nat Commun
; 11(1): 4903, 2020 09 29.
Article
in En
| MEDLINE
| ID: mdl-32994412
ABSTRACT
The CRISPR-Cas9 system has increased the speed and precision of genetic editing in cells and animals. However, model generation for drug development is still expensive and time-consuming, demanding more target flexibility and faster turnaround times with high reproducibility. The generation of a tightly controlled ObLiGaRe doxycycline inducible SpCas9 (ODInCas9) transgene and its use in targeted ObLiGaRe results in functional integration into both human and mouse cells culminating in the generation of the ODInCas9 mouse. Genomic editing can be performed in cells of various tissue origins without any detectable gene editing in the absence of doxycycline. Somatic in vivo editing can model non-small cell lung cancer (NSCLC) adenocarcinomas, enabling treatment studies to validate the efficacy of candidate drugs. The ODInCas9 mouse allows robust and tunable genome editing granting flexibility, speed and uniformity at less cost, leading to high throughput and practical preclinical in vivo therapeutic testing.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Non-Small-Cell Lung
/
Drug Discovery
/
CRISPR-Cas Systems
/
Gene Editing
/
Lung Neoplasms
Type of study:
Evaluation_studies
/
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2020
Document type:
Article
Affiliation country:
Suecia