Genotoxicity profiling reveals distinct platform-and cell type-specific effects in therapeutic gene editing for genetic hyperinflammation - PubMed
3 days ago
- #Genotoxicity
- #Hyperinflammation
- #Gene Editing
- Cytosine base editing (CBE) corrected a mutation in the Unc13d locus in Jinx mice, a model for familial hemophagocytic lymphohistiocytosis type 3 (FHL3).
- Editing efficiency ranged from 62% to 89% in fibroblasts, T cells, and hematopoietic stem cells (HSCs), restoring gene function and protecting mice from hyperinflammation after HSC transplantation.
- Genotoxicity analysis showed CBE causes broader off-target edits and more structural variants compared to CRISPR-Cas9, with chromosomal translocations varying in stability across cell types.
- The study supports base editing as a therapy for genetic hyperinflammation but highlights the need for context-specific safety assessments for clinical use.
- Authors disclosed multiple financial interests and patents related to gene editing technologies, including conflicts of interest with various biotech and pharmaceutical companies.