Overview
- UT Austin researchers reported the results Monday in Nature Structural & Molecular Biology, with support from NIH’s NIGMS and a partnership with Metagenomi.
- The team’s Al3Cas12f RKK variant raised genome-editing rates in a human leukemia‑derived cell line from under 10% to over 80%, reaching 90% at one target site.
- Cryo‑electron microscopy and machine‑learning models showed the enzyme has an expanded internal interface that makes the complex stable and largely preassembled in cells.
- Al3Cas12f outperformed two other compact Cas12f enzymes recently used by AAV in mouse studies, pointing to a stronger candidate for future therapeutic development.
- Researchers plan to package the nuclease into AAV next to test in‑body delivery, a key step that could move gene editing beyond ex vivo procedures limited to blood or bone marrow.