To achieve the optimal gene editing solution for each disease, we use protein engineering and directed evolution to create the best nuclease available for each specific indication, optimize the gene editing process for that target, and develop a custom drug composition with ultra-high target specificity and elimination of off-target effects.
And if we don’t have the right nuclease, we will go back to the discovery process and find it.
We start by analyzing the disease characteristics, mechanism of action, and genetic alterations, then design an editing strategy that would address as much of the patient population as possible.
- Genetic analysis (Pseudogenes, copy number)
- Required editing (KI, KO)
- Design specific editing strategy
- Select and test guides
- Discover and test nucleases
- Verify editing on genomic, mRNA and protein levels
- Verify functional output in model cells
- Verify functional output in patient-derived cells
- Determine off-targets, inversions and translocations
The most effective strategy moves into Lead Optimization where it is optimized through protein engineering, guide design and library selection.
- Optimize guide per target
- Optimize nuclease per target
- Protein engineering
- Libraries selections for variants
- Monitoring on and off-target
- Finalize composition
- Pack composition in a delivery vehicle
- Optimize per delivery vehicle
During Development, the gene editing strategy is validated on patient-derived cells.
- POC in-vivo
- Process development
- Scale-up and manufacturing
- Regulatory submission
- Tox studies
- Large animals
- Clinical development