Template-independent genome editing and restoration for correcting frameshift disorders - PubMed
4 hours ago
- #frameshift mutations
- #TIGER
- #genome editing
- TIGER (Template-Independent Genome Editing for Restoration) is a platform for correcting frameshift mutations.
- Frameshift mutations account for over 20% of Mendelian inherited diseases.
- TIGER uses a scoring system for guide RNA (gRNA)-Cas9 outcomes to improve therapeutic efficacy.
- Approximately 75% of deletion and 50% of insertion mutations produced ≥30% in-frame products, sufficient for phenotypic restoration.
- In a mouse model of deafness, TIGER restored hearing thresholds to wild-type levels with ~90% of in-frame edits being wild type.
- The inDelphi algorithm was retrained to predict therapeutic gRNAs for single-nucleotide frameshifts.
- TIGER provides a broadly applicable strategy for in vivo correction of inherited frameshift diseases.