This week, I’m excited to highlight two recent breakthroughs in CRISPR research that caught my attention:
?? BEAM Therapeutics' Phase 1 clinical data for BEAM-302: This novel base-editing therapy uses a Cas9-deaminase fusion to precisely target and correct the PiZ mutation responsible for alpha-1 antitrypsin deficiency (AATD). Patients received escalating doses (15, 30, and 60 mg) to evaluate in vivo editing efficiency. Remarkably, at the highest dose (60 mg), BEAM-302 increased total AAT levels from 4.4 μM to 12.4 μM, clearly surpassing the therapeutic threshold of 11 μM. Importantly, the treatment was well-tolerated, highlighting its potential as an effective genetic correction strategy for patients. While base editors can introduce unintended edits, these initial results are highly promising. I’ll be watching closely as PRIME Medicine also enters this space with RT-based editors, potentially offering enhanced precision.
See these results here: https://lnkd.in/gQXZ-5JS
?? Innovative research from the labs of Dave Savage and Jennifer Doudna (co-founders of Scribe Therapeutics) Their recent preprint, “Latent activity in TnpB revealed by mutational scanning,” provides an outstanding example of engineering CRISPR enzymes from modest baseline activity to high efficiency. TnpB, a compact RNA-guided nuclease and evolutionary ancestor of Cas12, was systematically improved using deep mutational scanning and yeast-based potency assays. The researchers identified specific mutations dramatically enhancing TnpB’s nuclease activity. By combining several beneficial mutations, they created an optimized “enhanced TnpB” variant, achieving up to 50-fold increased activity in plant systems —a reasonably respectable ?? leap in enzyme efficiency.
This research is a fantastic showcase of how systematic mutational scanning and combinatorial engineering can substantially enhance CRISPR enzyme performance—an approach we regularly utilize at Scribe Therapeutics to rapidly building powerful new genome-editing tools with improved therapeutic characteristics. Check it out: https://lnkd.in/gnbdhjGq.
Why I like this work: beyond showcasing TnpB as an exciting new small CRISPR enzyme, this study provides a clear playbook for modern molecular engineering. Comparing this work with others in the field, it is clear that comprehensive mapping of protein & RNA variants can surpass the effectiveness of both targeted mutagenesis and assay-na?ve AI strategies. Plus it's just more fun!
Check out these results here: https://lnkd.in/gnrabq_8
Together, these studies reflect the ongoing, vibrant evolution of CRISPR technology, driven by thoughtful scientific and engineering approaches.
