CRISPR/Cas9 is a powerful tool for elucidation of resistant mechanisms, identification of new targets, as well as a potential cancer therapy. In this thesis, we aimed to explore the potential of CRISPR/Cas9 for discovering therapeutic targets as well as for cancer therapy. To this end, we first reviewed the applications of CRISPR/Cas9 in the identification of new cancer targets, drug resistance, and cancer therapy. Later, we used CRISPR/Cas9 to knockout EGFR from different cancer cells, investigated the alterations of other Her family receptors, downstream signaling and the interactions of other receptors, including CXCR7, vEGFR, and PDGFR. Despite the rapid development of CRISPR/Cas9 technique, the gene editing potential of CRISPR/Cas9 is not yet sufficient enough for cancer therapy. Therefore, we sought to improve the CRISPR/Cas9 gene editing efficiency by altering the chromatin state through modulation of the HDAC and HAT activity. We provide a practical option for improving gene editing efficiency through chromatin de-condensation using HDAC inhibition. We have set up a platform for screening the small molecular compounds for enhancing or inhibiting CRISPR/Cas9 activity. Using this platform, we have screened out a highly potent CRISPR/Cas9 inhibitor. This platform can be widely used for screening enhancers and inhibitors of nucleases mediated-gene editing for future studies.
|Kwalificatie||Doctor of Philosophy|
|Datum van toekenning||29-okt-2019|
|Plaats van publicatie||[Groningen]|
|Status||Published - 2019|