Discovery of a VHL-Based Molecular Glue Degrader Targeting GEMIN3 Using Picowell RNA-Sequencing
- Leveraging ultra-miniaturized microfluidics devices to facilitate unbiased RNA-seq screening of a biased E3-focused library to enable target-agnostic discovery of VHL MGDs
- Identifying dGEM3, a novel VHL molecular glue that targets the survival of motor neuron (SMN) complex member GEMIN3 for degradation
- Characterizing the GEMIN3 degron within its helicase ATP-binding domain and revealing how ternary complex kinetics impact degradation through cellular, biochemical, and biophysical assays
- Explaining how these findings provide insights into the re-programmability of VHL for novel targets using drug-like molecular glues