CRISPR Base Editing Correction of TGFBI Mutations in Autosomal Dominant Corneal Dystrophies.

ABSTRACT:

Purpose

Lattice and granular corneal dystrophy comprise two common TGFBI-associated autosomal dominant corneal disorders. Existing therapies are only temporizing and carry significant morbidity. Here, we develop a novel therapeutic approach using an adenine base editor (ABE) to correct common TGFBI mutations.

Method

We generated two human corneal epithelial (HCE) cell models harboring a copy of the most common disease-causing TGBFI mutations, R124C or R555W. These lines were electroporated with an ABE8e-NG-encoding mRNA and guide RNAs targeting the mutations. The resulting A•T-to-G•C editing efficiencies and off-target (OT) effects were assessed by amplicon sequencing. GFP-expressing adeno-associated viruses (AAVs) with different capsid types were transduced into HCE cells a

SUBMITTER: Chen J 

PROVIDER: S-EPMC12949465 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature