A split enzyme complex enabling precise gene editing
The ability to target DNA deaminases to specific loci in concert with CRISPR/Cas systems has opened up new frontiers with the potential to transform biology and medicine by allowing for precise genome editing. At the same time, current DNA “base editors” typically employ constitutively active DNA deaminases as part of the base editor complex, which does not permit temporal control over base editing and is associated with off-target effects that can limit their therapeutic applications.
Dr. Rahul Kohli and his team have developed an inducible base-editing complex that is designed to be controllable and potentially reduce off-target effects. The inducible complex is comprised of a DNA deaminase that is split into two inactive components and whose function can only be reconstituted when combined. The two inactive components are linked to a rapamycin-responsive dimerizing construct, and so the function of the split DNA deaminase can be reconstituted with the addition of rapamycin. The split deaminases have been used to demonstrate controllable base editing at target sites.
- Controllable base editing via rapamycin (or other rapalog molecule) treatment
- High base-editing efficiency upon induction
- Decreased overall off-target effects
Stage of Development:
- Reduction to practice
- In vitro Proof of Concept