The difference in one sentence
Zinc finger nucleases came first and were the first editing tool used in patients, back in 2009. They are hard to design, which is why CRISPR displaced them almost entirely. But they are small — and when the delivery vehicle has a strict size limit, small is worth a great deal.
| Aspect | CRISPR-Cas9 | Zinc finger nucleases |
|---|---|---|
| How it finds the target | A short RNA guide | Protein modules, each gripping about three DNA letters |
| Ease of design | Trivial | Difficult — adjacent fingers influence each other |
| Size | Large — strains AAV capacity | Compact — packages comfortably |
| Sequence restriction | Requires a PAM | None, in principle |
| Clinical history | From 2016 onwards | From 2009 — the first human editing trials |
| Current use | Dominant | Where compact size or long safety history matters |
Sources
- New England Journal of Medicine (Tebas et al.) · 2014
Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV ↗