RT Journal Article
SR Electronic
T1 ObLiGaRe doxycycline Inducible (ODIn) Cas9 system driving pre-clinical drug discovery, from design to cancer treatment
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.06.028803
DO 10.1101/2020.04.06.028803
A1 Anders Lundin
A1 Michelle J. Porritt
A1 Himjyot Jaiswal
A1 Frank Seeliger
A1 Camilla Johansson
A1 Abdel Wahad Bidar
A1 Lukas Badertscher
A1 Emma J. Davies
A1 Elizabeth Hardaker
A1 Carla P. Martins
A1 Therese Admyre
A1 Amir Taheri-Ghahfarokhi
A1 Jenna Bradley
A1 Anna Schantz
A1 Babak Alaeimahabadi
A1 Maryam Clausen
A1 Xiufeng Xu
A1 Lorenz M. Mayr
A1 Roberto Nitsch
A1 Mohammad Bohlooly-Y
A1 Simon T. Barry
A1 Marcello Maresca
YR 2020
UL http://biorxiv.org/content/early/2020/04/07/2020.04.06.028803.abstract
AB 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. We have generated a tightly controlled ObLiGaRe doxycycline inducible SpCas9 (ODInCas9) transgene. Targeted ObLiGaRe resulted 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 can be utilized for robust and tunable genome editing allowing for flexibility, speed and uniformity at reduced cost, leading to high throughput and practical preclinical in vivo therapeutic testing.