Protein production: Purity
Misfolding proteins must be produced for study in the laboratory, but existing technologies are often not able to produce the relevant human forms, and generate only low quantities of impure material. Wren’s protein production platform is unique:
- Recombinant high-fidelity high-scale production of human misfolding proteins.
- Unique capability to produce fiercely challenging proteins, such as IAPP and TDP-43.
In vitro technology: Thio
Measurements of the misfolding process must be obtained across a wide-range of physiologically relevant conditions, yet existing approaches typically rely on non-physiological conditions to induce misfolding, and generate highly irreproducible data. Wren’s approach is different:
- Highly optimised, high-throughput, quantitative and reproducible assays providing the required signal-to-noise ratio for kinetic analysis.
- Proprietary protocols to monitor misfolding across physiological phase space.
Kinetic analysis: Kinetica
To understand misfolding diseases, experimental measurements must be connected to the individual microscopic steps in the reaction network, but current approaches ignore the complexity of protein misfolding. Wren’s network kinetics platform is a major step forward in the field:
- Integration of global experimental data sets to map the misfolding reaction network at the molecular level for each disease.
- Unique ability to modulate the population of any species of any protein that misfolds and aggregates.
In vivo technology: Fitness
Effects of drugs must be verified in model living systems, but significant noise levels and population variability makes it highly challenging to achieve adequate statistical power. Existing approaches typically involve manual measurements and small data sets. Wren has solved this problem:
- Proprietary massively parallel machine-vision C. elegans platform automatically monitors multiple phenotypes and biochemical readouts.
- Unique software and technology characterises output in thousands of animals from a library of custom transgenic strains.
Drug Optimisation: SKAR
Promising drug hits must be optimised to improve potency and ADMET, yet existing approaches typically identify “one off” hits that are challenging to rationally optimise. Wren’s Structure-Kinetics-Activity Relationship (SKAR) toolkit:
- Connects chemical features of drugs to their effects on specific kinetics rates within the reaction network.
- Unique ability to iteratively drive efficacy and specificity through lead optimisation.
Tracking protein aggregation in the laboratory and in patients is highly challenging, as it is currently only possible to detect either individual proteins or large aggregates of misfolded proteins, but not small and intermediate size species that may be particularly toxic. Wren’s antibody design platform transforms this situation:
- Third generation in silico antibody design platform generates antibodies against any epitope of an intrinsically disordered protein.
- Unique capability to generate conformation-specific antibodies, including against highly toxic protein oligomers.