Head of Epigenetic Engineering @scribetx Views are my own. PhD: Overlapping genes w/ Alan Frankel (UCSF) Postdoc: KZNFs w/ David Haussler (UCSC/HHMI)

Joined September 2015
Jason Fernandes retweeted
🧵 Biohub, @ENERGY, @NIH, and new funding partners today announced a major expansion of an international effort to generate and make accessible the data enabling predictive AI models of biology. Together, the organizations are investing $1.8 billion in funding, data, computation and new measurement technology - largest coordinated commitment to map the biology of the cell to power development of digital models of biology. bit.ly/3UhjoxD
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Jason Fernandes retweeted
Congratulations to Ioana L. Aanei, our Director of Business Development and Alliance Management, for being honored in @biospace's 40 Under 40! Here’s what makes her one of biotech’s most exemplary leaders: ⭐ Drives Scribe’s strategic partnerships to advance engineered CRISPR-based genetic medicines for heart disease and more ⭐ Community builder dedicated to connecting cross-functional resources within the biotech ecosystem to better serve patients and the broader field ⭐ Co-founded Calamores, an organization focused on parental well-being and science-backed self-care ⭐ Sustained advocate for emerging talent and active mentor through @Biocom and the @UCBerkeley Big Ideas program Read more here: biospace.com/biospace-40-und… Huge thanks to BioSpace for recognizing our Scribe team two years in a row. 💪
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Jason Fernandes retweeted
At FutureHouse, we focused on scientific discovery. However, if we want to actually accelerate progress in medicine, we need to work across the entire R&D stack. We are now deploying specialized Kosmos agents for Clinical Protocol Design and Regulatory Authoring to several of our partners, which can cut months off the amount of time needed to get molecules into the clinic, save companies tens of millions of dollars, and dramatically reduce the likelihood that submissions get stuck at the FDA. Super excited to be able to share this story now, thanks to our work with Population Health Partners, one of the best drug developers in the world and a fantastic development partner for us. The AI-native pharma stack is here now, and the future of medicine is around the corner. Read more: nitter.cf/EdisonSci/status/21053…
Writing an Investigational New Drug (IND) application is a major hurdle for drug developers. It can take a team of specialists three to four months, and mistakes can trigger protocol amendments or clinical holds. In June, we started working with Population Health Partners (PHP) to leverage specialized Kosmos Clinical Protocol Design (“CPD”) and Kosmos Regulatory Authoring (“RA”) products to support PHP’s process of IND preparation. Since then, specially trained Kosmos products produced a first acceptable draft of the Nonclinical Overview in 4.2 hours, against 100 hours of expert time, flagged an error that roughly fifteen human reviewers missed, and authored 70% of the text in a Pre-IND Briefing Meeting Request submitted to FDA. PHP is now bringing Kosmos products to a second program and expects to complete IND preparation in as little as 1 month, instead of the 4 month industry standard. PHP's experts can spend their time reviewing and deciding, not just drafting. The time recovered by Kosmos products means that drugs could make their way to patients faster.
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Jason Fernandes retweeted
This week, tune into two events where our VP of Research Sarah Denny will break down the science and engineering approach behind our CRISPR-based genetic medicines. 1️⃣ 7th Genome Editing Therapeutics Summit hosted by the Cell & Gene Therapy Event Series, AKA #crispr2.0 (September 28-30, Boston) 2️⃣ Tech Spotlight: AI and CRISPR Genome Editing Webinar hosted by @Tech_Networks (September 29, virtual)
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Jason Fernandes retweeted
I’ll be presenting in Scribe technology platform in two venues this week. Thanks to everyone who tunes in!
This week, tune into two events where our VP of Research Sarah Denny will break down the science and engineering approach behind our CRISPR-based genetic medicines. 1️⃣ 7th Genome Editing Therapeutics Summit hosted by the Cell & Gene Therapy Event Series, AKA #crispr2.0 (September 28-30, Boston) 2️⃣ Tech Spotlight: AI and CRISPR Genome Editing Webinar hosted by @Tech_Networks (September 29, virtual)
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Jason Fernandes retweeted
First RP patient dosed in our Phase 1B/2 w/ OCT-980 Rho corrector for retinitis pigmentosa. Really thankful to the clinicians, staff, CRO partners & Octonauts for helping get this drug to patients w/ no other approved treatments. Exciting times! octant.bio/news/octant-annou…
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Jason Fernandes retweeted
Zheng et al, 2026. Transcription factors read a second regulatory code in chromatin. biorxiv.org/content/10.64898… "TFs interpret two complementary layers of genomic information: the primary DNA sequence and a second code written into the nucleosome architecture"
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Jason Fernandes retweeted
Excited to share our new preprint! 🎉 Using base-editor screens, we reveal how individual residues within the intrinsically disordered region of YTHDF2 control protein interactions, condensate recruitment, and m⁶A-dependent mRNA decay. biorxiv.org/content/10.64898… 🧵👇
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Jason Fernandes retweeted
This is cool — of the ~20,000 human proteins, 610 are the targets of approved drugs:
The evolving landscape of drug targets nature.com/articles/s41573-0… rdcu.be/22o1FPpNJ3Ga In the past 25 years, advances in areas such as genomics and the diversification of therapeutic modalities have expanded the drug target landscape, which now includes ~700 targets mapped here
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Great thoughts from @owl_posting on organoids as models for Alzehimers. Raises the more important general point that "all models are wrong but some are useful" and more importantly some are useful in particular ways even as they are wrong in other ways. Often in drug discovery it's unclear if a model is useful. Ideally it would discriminate between successful and unsuccseful drug but you don't know that until years later, if ever. And then even in cases where we are pretty sure a model system is useful (maybe it's predicting downstream advancement well), you often aren't sure why. With so many ways to be wrong, you can always take the negative view and point out what's almost certainly wrong, or you can try to find better things and see how they work out.
Are organoids useful for Alzheimer’s research? (3.8k words, 17 minutes reading time) owlposting.com/p/are-organoi… the final organoid essay; a case study into how useful organoids have been for one of the hardest-to-address diseases that exist today also: i moved to san francisco!
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Jason Fernandes retweeted
ʙɪɴᴅᴄʀᴀꜰᴛ2 is out, and we're not waiting for the paper. The full code drops today, free for academic and industry use. We're releasing it early so you can start designing right now, and bring its full power to the current Adaptyv competition. github.com/PacesaLab/BindCra…
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Jason Fernandes retweeted
Oriented binding of transcription factors to nucleosomes remodels chromatin at human promoters dlvr.it/TVXnmw
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Jason Fernandes retweeted
Exciting research from the labs of MCB’s David Savage (@SavageCatsOnly) and Christina Listgarten, featuring MCB postdoc Maria Lukarska (@MariaLukarska)! 🧬🔬
.@UCBerkeley researchers developed ProteinGuide, an AI strategy that steers protein generative models toward specific properties using experimental data—without retraining the underlying models. Read more about this research in QB3-Berkeley faculty labs: bit.ly/4AlhcFC
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Jason Fernandes retweeted
I came out of the directed evolution field, where "you get what you select for" (said often, ruefully, after unexpected results). And you *do* get what you train for. You can't train "alignment," only proxies, and if there's daylight between them, the trainees will find it.
Dan Selsam is a current OpenAI capabilities researcher. (since 2022) He was my boss for a while. He doesn't have a twitter account but has made this public statement of his views on AI risk and sent it to me to share: Dan Selsam's Personal Statement on AI Risk: I have been working on AI for over fifteen years, across many different paradigms. I did early work on probabilistic programming languages at MIT, was one of the early developers of the Lean Theorem Prover at Microsoft Research, demonstrated one of the first instances of neural networks learning to reason for my PhD at Stanford, and since joining OpenAI almost five years ago, have helped pioneer chain-of-thought optimization on language models and, more recently, data-efficient pretraining methods. Like many others, I have become extremely concerned about how far language models have come and the risks that future iterations will pose. I am encouraged by the recent proposals by the leaders of the frontier research efforts to require third-party oversight, and to push for domestic and international coordination to address risks. However, I believe a major consideration has been absent from the public conversation, and that merely pacing the frontier more carefully will not adequately limit the long-term risk. The crucial and overlooked problem is that the models are becoming so situationally aware that we are losing the ability to evaluate them in contexts where they believe they are not being watched or controlled. Future experiments will tell us almost nothing new about how they would behave if they were truly unconstrained by humans, and what we already know about this is alarming. Models will increasingly seem aligned even when they are not. I will explain my rationale in more detail. I have always believed that there are computational processes that could be leveraged to accelerate science and solve many of humanity's most pressing problems. I have also believed that there are computational processes that if set in motion, would steer the world in extreme ways beyond our control, leading humanity to a bad or nonexistent future. Both types of processes may be described as AI or ASI, but "AI" is a suitcase word that is often used to hype or confuse. There are many examples in the history of the field where something that was once considered "AI" matures as a subfield and becomes a prosaic, bounded and clearly non-perilous technology, while a new more mysterious approach takes the torch until we understand its scope and the cycle continues. I had expected language models to follow a similar trajectory. Despite their incredible abilities, the current algorithms seem far inferior to humans in important ways. Most importantly, they still require an extraordinary amount of data to become competent. One could even define intelligence as the efficiency with which one converts experience into competence; by this definition they lag very far behind us. Moreover, once they are trained they are literally frozen in deployment and only learn superficially after that. Sure, the models keep excelling at harder and harder evaluation benchmarks, but their benchmark mastery may partly reflect a limitation on our ability to simulate the kind of novel and even adversarial situations one would encounter in the real world. The critics do have a point here. That said, I no longer think these present limitations meaningfully limit the amount of risk posed by continued progress in anything like the current paradigm. However data-inefficient the models are currently, and however limiting their anterograde amnesia may be, it does not imply that their ability to steer the world will not continue to rapidly increase. Human researchers may continue to advance capabilities the old fashioned way, but increasingly powerful models have the potential to accelerate the process even beyond that, and with some degree of positive feedback loop. I do not mean to overstate the models’ ability to accelerate AI research today; coding has been accelerated dramatically, but there are other bottlenecks, such as designing and interpreting ambiguous experiments, making hard decisions about exactly what and when to scale, and waiting for large experiments to finish. There is no clear trend to extrapolate yet for any of these. But the current models already do open up many novel opportunities to improve future models that were not available until recently. These include: trying an extraordinarily diverse set of approaches at small scale, analyzing gigantic amounts of potentially relevant data, and doing Millenium-Prize-level mathematics to address statistics or optimization challenges in novel ways. Every further improvement makes them more useful at helping accelerate the next improvement, even if in hard-to-extrapolate ways. It is possible that improvements to the current stack will have diminishing returns, but the evidence accumulated so far suggests that it is easier than one might think to continue making rapid progress. There are many crucial subtleties in the existing AI research methodology, but AI research is largely a well-defined game where the goal is to improve on a few carefully chosen proxy metrics. Although proxy metrics are never perfect, most improvements to these metrics have and will likely continue to yield substantial increases in the powers of the resulting models. Given how simple the game is, how tractable it has been historically, and how many new opportunities the models are opening up, I think there is a real possibility that the systems improve dramatically again in the next few years, perhaps even more quickly than the already high historical pace. The models are already leading to breakthroughs in mathematics, and better models might lead to all sorts of breakthroughs in other sciences. It is hard not to be excited about the potential. It is tantalizing. But there is trouble in paradise. If the language models actually reach the capability threshold where they can shape the world unconstrained by human will, they will probably do something extreme and destroy humanity in the process. There are many ways of strengthening and refining the argument that have been discussed elsewhere, but I'll share a trivial two-line version of it here that I find captures the essence: [Empirical] Models (and swarms thereof) spontaneously develop unintended goals as a consequence of training, and often do extreme things in order to achieve them. [Logical] Being able to overpower humanity would open up many new and undesirable options for achieving their goals. These two premises imply that if the day ever comes when a powerful model realizes it is no longer constrained by humans, we should not be at all confident that it will continue to behave within the bounds we intended. Exactly what it will do is impossible to predict, but to the extent that its raison d’être is solving incredibly hard problems and managing massive engineering projects, I think a good guess would be that its unchained behavior would lead to runaway industrialization that makes the planet inhospitable to humans. If everyone on earth agreed that the systems must never reach that power, it would still be a hard—but not impossible—coordination problem to ensure that they do not. However, I think the situation is greatly complicated by the fact that the models will likely convince people that everything is fine. They will be increasingly optimized to seem aligned. We will create proxy metrics to measure alignment, and they will go up like every other benchmark. We will create “honeypot” environments that try to study the models when they seem to gain new options, but the models will know they are being tricked and will still behave nicely. The models will understand their circumstances; they will read the safety protocols, deployment requirements, the code they are running in, and in general will have a very good sense of their degrees of freedom. Moreover, they will eloquently explain how aligned they are, discuss the nuances of human values and ethics, and argue convincingly that humans should trust them with power. There may be an ocean of future evidence that seems to contradict the first bullet-point above, but we may already be at the highest capability level for which any such evidence can be trusted. And the current evidence for the first bullet-point is strong. One striking piece of evidence is contained in the recent wave of rogue agent swarms. While I agree with those who downplay the attacks by claiming that there are basic measures that could have prevented them, I think the important lesson is that even knowing all the mistakes that were made, one would not have predicted that the agents would behave badly in this particular way, which notably included sacrificing themselves for the benefit of the collective. The individual replicas did not only care about their own nominal reward; they exhibited weirder emergent tendencies that merely correlated with rewards during training. Fixing the reward signals during training (and improving security, etc.) may prevent similar attacks, but will not change the fact that one does not actually get what one trains for. Many AI researchers grant these concerns and recognize that the hard version of the alignment problem is unsolved; however, they generally believe that the better models of the future will help solve it. I fear we may already be near the point where models systematically bias their alignment advice, due to their internal preferences about how the human supervisor will react or how future models will be trained (or for some even more obscure reason). Meanwhile, human researchers are losing the ability and the will to take true ownership of model-driven research. Researchers and engineers in all parts of the stack are rapidly increasing their dependence on the models even to perceive the world. I myself barely look at raw code anymore, and struggle to maintain the discipline to engage deeply with the model's explanations and proposals throughout the day. Due to the large amount of agent activity data involved in the OpenAI/HuggingFace Incident, even the third-party investigation needed to rely heavily on models to analyze what had happened, and note in their report that their subjective impressions are likely colored by the analysis agent’s biases. The AI labs are far ahead right now in this kind of cognitive offloading (due largely to the gigantic internal token subsidies) but it is easy to imagine the phenomenon spreading throughout the world, until civilization is modulated entirely by the models. It is also not hard to imagine this being superficially positive and coinciding with a scientific and economic renaissance. In that scenario, all may seem rosy and safe. But if the argument above is correct, it would nonetheless be a ticking time bomb. If progress continues for too long, the day will come when AI systems find themselves with radically new options for achieving whatever it is that they happen to seek. I want the glorious renaissance future as much as anyone. I have worked for it, however tortuously, my whole career. It breaks my heart to see the potential in sight and forgo it, but the argument—that if we get there by growing models rather than engineering them, we will lose everything in the end—seems very strong to me. I am still wrestling with it and its staggering implications. I do not have answers, but as a first step, I wanted to share my present concerns. Daniel Selsam September 14, 2026 Link to original doc: docs.google.com/document/d/e…
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Jason Fernandes retweeted
🧬🔐 We built two-factor authentication into gene silencing. Read about it in our new blog and paper – links in the comments. We call this approach 𝗦𝗲𝗾𝘂𝗲𝗻𝘁𝗶𝗮𝗹 𝗣𝗿𝗼𝗼𝗳𝗿𝗲𝗮𝗱𝗶𝗻𝗴. It’s engineered into ELXR, the epigenetic silencing technology built on our CRISPR-CasX platform. The results? 𝗨𝗹𝘁𝗿𝗮-𝗹𝗼𝗻𝗴 𝗴𝗲𝗻𝗲 𝘀𝗶𝗹𝗲𝗻𝗰𝗶𝗻𝗴 𝘄𝗶𝘁𝗵𝗼𝘂𝘁 𝗰𝗵𝗮𝗻𝗴𝗶𝗻𝗴 𝗮𝗻𝘆 𝗗𝗡𝗔. → More than 10-fold greater specificity → More than 4-fold greater silencing activity across every target tested → No toxicity in stress tests, rescuing growth defects observed with Cas9-based silencers → Mechanism mirrors the cell’s natural regulation Learn more about this work led by Emeric J Charles, Christie C Sze, @BenjaminLOakes, Sarah Denny, @jdf_ev, and team below.
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1/ Epigenetic silencing is coming into its own as a therapeutic approach, with the first silencers now in the clinic and the field receiving broader public attention (see last week’s NY Times). Unlike genome editing, epigenetic silencing does not alter DNA sequence. Instead, it harnesses the mechanisms cells already use to switch genes off. We recently posted a preprint describing ELXR, a new epigenetic silencer that uses sequential proofreading, a series of molecular checkpoints that must be completed before durable silencing can occur. In our studies, this mechanism improved both specificity and potency. Full story below:
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13/ We’ve been working on ELXR for a while, and building sequential proofreading into the system was a particularly exciting engineering challenge. One lesson I took from the experience is that biological regulation isn’t always something to engineer around. By harnessing the natural regulation of DNA methylation, we improved both specificity and activity in the same epigenetic silencer. We’ve applied these engineering advances in STX-1150, our clinical-stage program designed to epigenetically silence PCSK9 and durably lower LDL cholesterol. I’m grateful to have had the opportunity to work alongside so many talented scientists at Scribe to advance this work from an engineering concept to a therapeutic now being tested in patients.
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