Benjamin L. Oakes

Advancing CRISPR Cures Requires Cross-Sector Collaboration Amid a challenging gene editing climate, partnerships between researchers, regulators, and industry remain crucial for pushing CRISPR cures to the clinic.

“In reality, you’re seeing nothing but good data come out of the CRISPR space. I don’t believe the ability to cure patients is going anywhere.” – @benjaminloakes.bsky.social, Scribe CEO in GEN on delivering the full promise of #CRISPR

Read more here and our 🧵: www.genengnews.com/topics/genom...

We’re pleased to announce the achievement of a success milestone in our collaboration with Prevail Therapeutics, a part of @elilillyandcompany.bsky.social’s Gene Therapy Division, to develop in vivo #CRISPR-based therapeutics for neurological and neuromuscular disorders.

Highlights below 🧵

The goal is to develop therapeutics that are broadly effective and safe enough for all. But financial access is complex—most payor systems don’t know how to reward long-term health. We’ll need to push the system to redefine value as not just treating illness, but preventing it before it starts.

This future is real. It’s not even decades away, it’s within reach.

🔬Building this future is what we’re doing at Scribe.🔬

So yeah, I’m likely to keep saying it:

Get excited. 🚀 Spread the word. Support genetic medicine and help shape what comes next. The future of health is already on its way.

🌍 Universal
Safe enough to be standard. Broad enough to prevent disease across the board. We’re talking about stopping ASCVD, stroke, diabetes, kidney disease — all as part of routine care.

⚡ Liberating
Treatments won’t be daily pills or ongoing injections.
You’ll walk into a clinic, get a highly durable treatment, and walk out fundamentally healthier. Transformative care with no upkeep required.

🧬 Preventive
We’ll use genetic insights to eliminate disease before it starts.
Imagine taking the DNA of your healthiest 100-year-old relative — the one who never had heart disease or cancer — and making it yours. That’s the promise of genomic medicine: everyone gets to win the genetic lottery.

The future of medicine is bright — and it’s going to look radically different from today.
It’ll be:

🧬 Preventive
⚡ Liberating
🌍 Universal

This isn’t science fiction — it’s what we’re building at @ScribeRx. Let me break it down 👇

#LpaAwarenessDay

Cardiovascular disease is the leading cause of death worldwide, claiming 18 million lives each year.

Did you know that 1 in 5 people have high levels of Lp(a) or lipoprotein(a), which significantly increases the risk of heart disease?

Check out this 🔥 work here! www.biorxiv.org/content/10.1...

Why I like it: This study provides a clear playbook for modern molecular engineering. Comparing this work with others in the field, it is clear that comprehensive variant mapping surpasses the effectiveness of targeted mutagenesis and assay-naïve AI engineering approaches. Plus it's just more fun!

Scribe → Platform

This work elegantly demonstrates how systematic variant scanning, and combinatorial assembly, can supercharge CRISPR and is similar to engineering approaches we utilize @scribetx.bsky.social for rapidly building powerful new CRISPR tools. Check it out: www.scribetx.com/platform

This meticulous screening reveals specific mutations that greatly enhance TnpB’s nuclease activity. By stacking beneficial single mutations into one optimized variant (“enhanced TnpB”), they achieved up to 50-fold higher activity in plants—a reasonably respectable 🤯 leap in enzyme efficiency.

Quick background: TnpB is a compact RNA-guided nuclease and the evolutionary ancestor of Cas12. In this work, the team uses deep mutational scanning with a yeast-based cleavage assay to profile every RNA & protein variation.

Next, the preprint “Latent activity in TnpB revealed by mutational scanning” @brittneywthornton.bsky.social & @rfw.bsky.social et al., coming out of the Doudna & Savage labs. This work beautifully illustrates how holistic molecular engineering systematically improves CRISPR molecules

Importance: These data highlight CRISPR’s immense potential for in vivo cures. Yet, as base editors may create unintended edits, the exact correction efficiency in this trial is uncertain. PRIME Medicine recently entering this disease area with RT-based editors may offer additional precision.

Beam Therapeutics Announces Positive Initial Data for BEAM-302 in the Phase 1/2 Trial in Alpha-1 Antitrypsin Deficiency (AATD), Demonstrating First Ever Clinical Genetic Correction of a Disease-causin... Single Dose of BEAM-302 Led to Durable, Dose-dependent Increases in Total and Functional Alpha-1 Antitrypsin (AAT), Production of Corrected M-AAT, and...

At the highest dose, BEAM-302 boosted total AAT from 4.4 µM to 12.4 µM, surpassing the perceived therapeutic threshold of 11 µM. Importantly, the treatment appeared well-tolerated and is promising as correction strategy for AATD patients in need. Check it out: www.globenewswire.com/news-release...

First, let’s dive into BEAM’s results: this base-editing therapy uses a Cas9-deaminase fusion to target and mutate the PiZ mutation causing alpha-1 antitrypsin deficiency (AATD). Patients received doses of 15, 30, & 60 mg to assess in vivo editing efficacy.

This week, I’ll highlight two recent CRISPR advances: 1) BEAM’s exciting Phase 1 clinical data for BEAM-302. 2) Impressive work from the labs of Scribe’s co-founders @savagecatsonly.bsky.social & @doudna-lab.bsky.social —providing a textbook example of engineering CRISPR enzymes from zero to hero.

CRISPR’s cardio catch-all drives a biotech’s broad potential Scribe Therapeutics hopes to prevent cardiometabolic diseases by targeting underlying causes with CRISPR technology.

From an interview with our CEO @benjaminloakes.bsky.social, PharmaVoice spotlighted our work engineering #CRISPR genome editing and epigenetic silencing platforms to target cardiometabolic disease.

Read the story about our lead asset and progress: www.pharmavoice.com/news/crispr-...

Don’t miss @jdfev.bsky.social's late-breaking talk at @keystonesymposia.bsky.social today!

📣 Symposia Spotlight
🪧 Engineering of Next Generation Epigenetic Editors for Enhanced Durable Repression in Non-Human Primates
🕒 3:00-4:30 p.m. GMT
📍 INEC Main Auditorium

💡 Want to see how these breakthroughs will help to shape the future of medicine? Don’t miss Jason Fernandes’ presentation at Keystone: Precision Genome Engineering: Translating the Human Genome to the Clinic, Tomorrow, March 4, 3:00-4:30 p.m. GMT! #KSGenomeEng25

🎤 In fact, this week at Keystone Symposia, we’re unveiling major advancements in epigenetic therapies. Our engineering engines have built thousands of possibilities, uncovering stronger, safer, and more precise therapeutics.

Epigenetic editors are a gentler form of gene editing But they may prove just as powerful

📰 It was great speaking with Ida Emilie Steinmark for The Economist’s The Age of CRISPR. The piece highlights how Scribe's epigenetic editors could give everyone access to protective genetic traits and dramatically reduce ASCVD risk. www.economist.com/technology-q...

🧬 In the near future, my hope is that we can all win the genetic lottery for health—not by chance, but by design. At Scribe, we’re focused on making genetic medicines safe enough for disease prevention at scale and moving beyond gene editing into epigenetic editing.

As someone with close family affected by ASCVD—and therefore at high risk myself—this mission is personal, urgent and real. We will solve this.

Explore our vision for the future of ASCVD treatment—and, more importantly, prevention—below.

As someone with close family affected by ASCVD—and therefore at high risk myself—this mission is personal, urgent and real. We will solve this.

Explore our vision for the future of ASCVD treatment—and, more importantly, prevention—below.

The reverse transcriptase domain of prime editors contributes to DNA repair in mammalian cells - Nature Biotechnology DNA repair activity of reverse transcriptase may negatively affect prime editing precision.

Why I like it: This work forces me to rethink the global off-target effects of prime editing, much like recent base editing insights. It’s also a call to engineer smarter tools.

Check it out: www.nature.com/articles/s41...

When Zheng et al. look more deeply at this question they find the RT domains (fused to Cas or not) cluster at DNA breaks faster than endogenous DNA repair proteins and alter repair outcomes by inserting random nucleotides. This reminds me of how Base Editors can randomly alter DNA R-loops or ssRNA.

Prime editors are often touted as super precise systems but here’s a twist: past studies like Gurnewald et al. (2023) and Liu et al. (2022) show they work even without the RT fused to Cas9. That should challenge our assumptions—we don't fully understand how/where these molecules work in the cell.