Identifying Novel Targets and Disease Drivers with in vivo CRISPR Screening
In vivo CRISPR screening provides unparalleled insights into tumor biology by capturing the intricate interactions of the in vivo environment, such as immune responses and systemic signaling. Unlike traditional in vitro approaches, a CRISPR screen in vivo using xenograft models allows researchers to study biological processes under realistic physiological conditions.
The case study presented in this poster explores tumor survival mechanisms by transfecting lung cancer A549 cells with 3,188 single guide RNAs targeting tumor suppressor genes. Cells were implanted into mice, and tumors were treated with the kinase inhibitor Trametinib, followed by tissue collection at multiple time points. The genetic variations that allowed the tumors to resist Trametinib treatment, and thus provided a survival advantage, were identified via sequencing and MAGeCK analysis.
This study showcases the power of in vivo CRISPR screening to discover novel anti-cancer targets, setting the stage for next-generation therapies.