Electrostatic remodeling of TadA8e* eliminates ABE8e genome-wide off-target effects - PubMed
5 hours ago
- #gene editing
- #off-target effects
- #base editor
- ABE8e has high efficiency but substantial genome-wide off-target edits, including in oncogenes and tumor suppressors, posing risks for clinical translation.
- Researchers developed erABE by electrostatically remodeling TadA8e, reducing ABE8e's off-target activity by ~36.5-fold to background levels while maintaining editing efficiency.
- In mice, a single low-dose of erABE in lipid nanoparticles led to sustained ~90% reduction in plasma PCSK9 protein and ~60% reduction in LDL cholesterol for at least 6 months.
- erABE also effectively suppressed PCSK9 expression in human liver organoids, demonstrating safety and durable therapeutic potential for clinical genome-editing.