Artios is developing novel anti-cancer medicines targeting the DNA damage response. To enable this, we developed a range of novel assays to measure cellular DNA repair activity. These assays had a major impact on our programs, leading to clinical-stage assets being tested in patients with high unmet medical needs.
Accurately measuring on-target cellular activity is essential for progressing novel targeted therapeutics. Generating assays for DNA repair factors with the required properties for fueling an efficient drug discovery campaign has been challenging, whether is need for high-throughput, robust signal-to-noise, rapid turnaround, and ideally, portability to different biological systems. We have developed a suite of robust, quantitative, and titratable luminescence-based reporter assays to measure the proficiency of four major double-strand break repair pathways, homologous recombination, non-homologous end joining, microhomology-mediated end joining, and single strand annealing.
These reporter assays are validated as reading out pathway-dependent repair, are sensitive to pharmacological modulation, and have a fast turnaround time. The repair substrates we have developed are extrachromosomal, so they can be transiently transfected into models of interest and easily scaled into a high-throughput format. We believe our assay systems have an important place in enabling DDR drug discovery, but also in furthering our understanding of DDR biology more broadly.
In this respect, we hope the methods help accelerate the identification and prosecution of new drug targets, leading to medicines for diseases such as cancer where there high unmet medical need.
