Ever wondered why CRISPR gene editing works great in lab cells but faces hurdles in the brain? A groundbreaking study from Nature Communications reveals key insights into DNA repair in postmitotic neurons—non-dividing cells like those in our brains that must endure lifelong damage.
🔬 Key Findings:
- Using virus-like particles (VLPs) to deliver Cas9, researchers compared editing in human iPSCs (dividing cells) vs. iPSC-derived neurons.
- Neurons accumulate indels (insertions/deletions) slowly—over weeks, not hours—due to prolonged DSB (double-strand break) repair signals.
- Unlike dividing cells, neurons upregulate unexpected DNA repair genes (e.g., RRM2, typically S-phase restricted) in response to Cas9, even without cuts.
- Inhibiting factors like RNR (ribonucleotide reductase) boosts editing efficiency by ~50% and shifts outcomes toward precise deletions, validated in neurons, cardiomyocytes, and primary T cells.
Why it matters: This could revolutionize therapies for neurodegenerative diseases (e.g., Huntington’s) by controlling repair for safer, more effective edits. Neurons’ unique response highlights why we can’t just apply dividing-cell rules to the brain.
The study also introduces “all-in-one” particles combining Cas9 with RNAi to tweak repair in real-time— a new tool for precision genome editing!
đź“– Read the full paper: https://www.nature.com/articles/s41467-025-66058-3
