Jeff Ruffolo (@jeffruffolo) header
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Protein Design / ML @ProfluentBio | Molecular Biophysics PhD @JohnsHopkins

San Francisco, CA
Joined November 2014
Photo by Jeff Ruffolo (@jeffruffolo)Photo by Jeff Ruffolo (@jeffruffolo)Photo by Jeff Ruffolo (@jeffruffolo)Photo by Jeff Ruffolo (@jeffruffolo)Photo by Jeff Ruffolo (@jeffruffolo)Photo by Jeff Ruffolo (@jeffruffolo)Photo by Jeff Ruffolo (@jeffruffolo)Photo by Jeff Ruffolo (@jeffruffolo)Photo by Jeff Ruffolo (@jeffruffolo)Photo by Jeff Ruffolo (@jeffruffolo)
Jeff Ruffolo retweeted
Heading to Summer RosettaCon next week to share my work from my time at @ProfluentBio Come listen to my talk about the encoder model Profluent-E1 on Thur at 1:30pm (“E1: Retrieval-Augmented Protein Encoders for Fitness and Structure Prediction”) and let’s chat after!
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I’m heading to ICML in Seoul with the @ProfluentBio team. If you want to talk protein design, generative models, or anything BioML, come find me! And if you want to meet the Profluent team, we're hosting dinners and doing coffee chats throughout the week. Sign up below.
The Profluent team will be at ICML in Seoul next week. Find us to chat, grab a coffee, or join us for dinner! We’d love to talk shop (protein language models, protein optimization, sequence-first methods vs structure-first). Basically, anything at the intersection of AI and biology. Want to grab coffee? Let us know here: forms.gle/yWQpAvLiQ1KfM85u7 Or want to hang out and chat over dinner? Reserve a spot at our table: luma.com/qpc1mfw9
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Check out @park_jungy's work on discovering symmetry groups with flow matching at ICML on Wednesday!
(1/8) Happy to share that our paper LieFlow has been accepted to #ICML2026. Symmetry is a strong inductive bias in ML, but you have to know the symmetry in advance. Can a model discover it directly from data, for both discrete and continuous groups? 🧵
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Jeff Ruffolo retweeted
AI has two modes in drug discovery. Accelerate: moving faster through the existing playbook. Unlock: opening frontiers that weren't possible before. Excited to announce Profluent is partnering with Eli Lilly, the global pharma powerhouse, to unlock breakthrough medicines for patients. It's a big deal beyond the numbers ($2.25B + royalties): we’ll get to use our frontier AI models and foundational datasets to design proteins focused on large gene insertion, a therapeutic moonshot. Proteins govern almost everything in biology. We've built a generalizable AI platform to design all proteins. Onward!
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Jeff Ruffolo retweeted
Today, @ProfluentBio and @EliLillyandCo announce a multi-$B partnership to use our AI models to design custom recombinases, a new class of gene editor capable of large-scale DNA editing across multiple diseases. I'm so proud of the team - Profluent is an n=1 company.
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This project is a clear expression of what generative protein models are best at. Train on nature's full catalog of sequences, learn the patterns underneath,  then design new proteins for problems nature didn't solve.
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With Lilly, we're applying that to recombinases, proteins capable of inserting kilobases of DNA into a genome and designed to target specific genetic disorders. Congrats to the whole team on this milestone!
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Excited to share that we’ll be working with @EliLillyandCo to develop AI-designed recombinases for genetic medicine.
Today we announced a landmark partnership with @EliLillyandCo to use our AI models to design recombinases for genetic medicine—a collaboration valued at up to $2.25 billion before royalties. The goal: use Profluent's AI models to design recombinase editors capable of inserting long stretches of DNA at precise locations in the genome. Read the press release for more: businesswire.com/news/home/2…
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We're hiring on my team at @ProfluentBio: Protein Design Scientist, Agentic Workflows. Protein language models learn the evolutionary rules of natural sequences, but turning that into a design pipeline that works end-to-end is a different problem. job-boards.greenhouse.io/pro…
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We're a small, interdisciplinary team — ML scientists, protein design scientists, biologists, bioinformaticians — and this person would work across all of those groups. High-ownership IC role where what you build goes directly into design campaigns that hit the lab.
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Looking for strong engineering, hands-on PLM experience, and real protein domain knowledge. If this sounds like your background, please reach out or apply directly!
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Jeff Ruffolo retweeted
Today we’re announcing $106M in new funding led by Altimeter Capital and Bezos Expeditions. This brings our total to $150M to scale our frontier AI models which make biology programmable. Our frontier models have generated functional proteins (Nature Biotech, 2023), created the first CRISPR system designed from scratch (Nature, 2025), and showed clear scaling behavior (NeurIPS spotlight, 2025). The opportunities ahead are unimaginable. If you’re excited by shaping the future of biology – join us in pushing the science forward. Forbes: forbes.com/sites/amyfeldman/… Press Release: businesswire.com/news/home/2… -- Nature Biotech, 2023: nature.com/articles/s41587-0… NeurIPS spotlight, 2025: biorxiv.org/content/10.1101/… Nature, 2025: nature.com/articles/s41586-0…
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Jeff Ruffolo retweeted
AI can bring high quality genetic tools within reach for rare diseases. Today, Profluent is partnering with the Rett Syndrome Research Trust (RSRT) to design personalized genomic medicines for Rett syndrome. Our aim is to engineer compact editors that can fit into a single AAV delivery capsid, a key step toward reaching the central nervous system. Once there, our editors will need to precisely correct recurrent MECP2 hotspot mutations that drive Rett syndrome pathology. Rare disease used to mean rare attention. Specialized genetic tools were reserved only for the most common conditions. AI is changing that, bringing state-of-the-art biotechnology to a rare neurodevelopmental disorder that touches families every day. Profluent and RSRT are excited to bring the ProGen3 model and the full strength of our platform to bear on Rett syndrome. We’re working relentlessly toward a future when AI helps to make the best science accessible to all patients. 🔗 reverserett.org/news/article…
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Jeff Ruffolo retweeted
Protein language models just got an upgrade. Meet Profluent-E1: a free, flexible, frontier protein sequence encoder. E1 is built with retrieval augmentation to learn from multiple sequences. Models trained over 4T tokens with only 150M-600M params, E1 is SOTA for zero-shot functional and unsupervised structural tasks. It raises the bar for protein representation learning and is freely available today.
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I’m excited to share Profluent-E1, our internal encoder model for protein sequences, with the protein-ML community! The E1 series of models can be used as a drop-in replacement to upgrade a broad range protein modeling and design of workflows. biorxiv.org/content/10.1101/…
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These evaluations are just the beginning. At @ProfluentBio, we’ve already found E1 to be a compelling alternative to existing encoders. Our hope in releasing these models is for others to boost their own workflows and provide feedback that helps us continue to push the frontier.
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