ObLiGaRe doxycycline Inducible (ODIn) Cas9 system driving pre-clinical drug discovery, from design to cancer treatment

Anders Lundin, et al.

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Received Date: 23rd March 20

Anders Lundin, Michelle J. Porritt, Himjyot Jaiswal, Frank Seeliger, Camilla Johansson, Abdel Wahad Bidar, Lukas Badertscher, Emma J. Davies, Elizabeth Hardaker, Carla P. Martins, Therese Admyre, Amir Taheri-Ghahfarokhi, Jenna Bradley, Anna Schantz, Babak Alaeimahabadi, Maryam Clausen, Xiufeng Xu, Lorenz M. Mayr, Roberto Nitsch, Mohammad Bohlooly-Y, Simon T. Barry, Marcello Maresca

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.

Read in full at bioRxiv.

This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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