CC-ABE

Stages

1. 1.
   split base editor design(library_design)

   This stage exists to address the size of base editors that exceeds AAV packaging capacity.

   Selection: Design split base editor systems that recruit deaminases to Cas9 nickase via coiled-coil heterodimers.

2. 2.
   cell-based activity evaluation across editor variants and contexts(functional_characterization)

   This stage checks whether the split architecture compromises editing performance before in vivo use.

   Selection: Assess whether CC-BEs maintain or improve editing efficiency relative to original unsplit base editors across various cell types and editing scopes.

3. 3.
   in vivo dual-AAV validation in mice(in_vivo_validation)

   This stage confirms that the split-editor strategy solves the delivery-size problem in an in vivo setting.

   Selection: Validate in vivo editing efficiency of CC-ABE by testing A-to-G conversion at Pcsk9 and Dmd in mice via dual-AAV vectors.

Steps

1. 1.
   Design split base editors by linking deaminase and Cas9 nickase modules through coiled-coil heterodimersengineered split editor systems

   Create base editor architectures that can bypass AAV packaging limits.

   The size of conventional base editors is presented as the primary barrier to in vivo AAV application, so the workflow begins with a split-design solution.

2. 2.
   Compare editing efficiency of CC-BEs against original unsplit base editors across cell types and editing scopessplit editor variants under evaluation

   Determine whether splitting preserves or improves editing activity before in vivo testing.

   The abstract indicates that activity must be maintained despite splitting, making this a necessary gate before animal validation.

3. 3.
   Validate CC-ABE in vivo by dual-AAV delivery and test A-to-G conversion at Pcsk9 and Dmd in micesplit editor delivered for in vivo validation

   Confirm that the split-editor strategy enables in vivo base editing under AAV packaging constraints.

   In vivo validation follows cell-based activity evidence because animal testing is used to confirm practical delivery and function after the lower-complexity activity checks.