BlankBio started from our PhD work in this area, which is open-sourced. There’s a model [2] and a benchmark with APIs access [0].
mRNA has the potential to encode vaccines, gene therapies, and cancer treatments. Yet designing effective mRNA remains a bottleneck. Today, scientists design mRNA by manually editing sequences AUGCGUAC... and testing the results through trial and error. It's like writing assembly code and managing individual memory addresses. The field is flooded with capital aimed at therapeutics companies: Strand ($153M), Orna ($221M), Sail Biomedicines ($440M) but the tooling to approach these problems remains low-level. That’s what we’re aiming to solve.
The big problem is that mRNA sequences are incomprehensible. They encode properties like half-life (how long RNA survives in cells) and translation efficiency (protein output), but we don't know how to optimize them. To get effective treatments, we need more precision. Scientists need sequences that target specific cell types to reduce dosage and side effects.
We envision a future where RNA designers operate at a higher level of abstraction. Imagine code like this:
seq = "AUGCAUGCAUGC..."
seq = BB.half_life(seq, target="6 hours")
seq = BB.cell_type(seq, target="hepatocytes")
seq = BB.expression(seq, level="high")
To get there we need generalizable RNA embeddings from pre-trained models. During our PhDs, Ian and I worked on self-supervised learning (SSL) objectives for RNA. This approach allows us to train on unlabeled data and has advantages: (1) we don't require noisy experimental data, and (2) the amount of unlabeled data is significantly greater than labeled. However the challenge is that standard NLP approaches don't work well on genomic sequences.Using joint embedding architecture approaches (contrastive learning), we trained model to recognize functionally similar sequences rather than predict every nucleotide. This worked remarkably well. Our 10M parameter model, Orthrus, trained on 4 GPUs for 14 hours, beats Evo2, a 40B parameter model trained on 1000 GPUs for a month [0]. On mRNA half-life prediction, just by fitting a linear regression on our embeddings, we outperform supervised models. This work done during our academic days is the foundation for what we're building. We're improving training algorithms, growing the pre-training dataset, and making use of parameter scaling with the goal of designing effective mRNA therapeutics.
We have a lot to say about why other SSL approaches work better than next-token prediction and masked language modeling: some of which you can check out in Ian's blog post [1] and our paper [2]. The big takeaway is that the current approaches of applying NLP to scaling models for biological sequences won't get us all the way there. 90% of the genome can mutate without affecting fitness so training models to predict this noisy sequence results in suboptimal embeddings [3].
We think there are strong parallels between the digital and RNA revolutions. In the early days of computing, programmers wrote assembly code, managing registers and memory addresses directly. Today's RNA designers are manually tweaking sequences, improving stability or reduce immunogenicity through trial and error. As compilers freed programmers from low-level details, we're building the abstraction layer for RNA.
We currently have pilots with a few early stage biotechs proving out utility of our embeddings and our open source model is used by folks at Sanofi & GSK. We're looking for: (1) partners working on RNA adjacent modalities (2) feedback from anyone who's tried to design RNA sequences what were your pain points?, and (3) Ideas for other applications! We chatted with some biomarker providing companies, and some preliminary analyses demonstrate improved stratification.
Thanks for reading. Happy to answer questions about the technical approach, why genomics is different from language, or anything else.
- Phil, Ian, and Jonny
founders@blankbio.com
[0] mRNABench: https://www.biorxiv.org/content/10.1101/2025.07.05.662870v1
[1] Ian’s Blog on Scaling: https://quietflamingo.substack.com/p/scaling-is-dead-long-li...
[2] Orthrus: https://www.biorxiv.org/content/10.1101/2024.10.10.617658v3
[3] Zoonomia: https://www.science.org/doi/10.1126/science.abn3943
anyg•3h ago
antichronology•2h ago
- mRNA therapies: These therapies deliver a synthetically created messenger RNA (mRNA) molecule, typically protected within a lipid nanoparticle (LNP), to a patient's cells. The cell's own machinery then uses this mRNA as a temporary blueprint to produce a specific protein.
The big example here is CAR-T therapy from Capstan which just got acquired for 2.1B. Their asset,CPTX2309 , is currently in Phase 1. Previously to do Car-T therapy you had to extract a patient's T-cells and genetically engineer them in a special facility. Now the mRNA gets delivered directly to the patient's t cells which significantly lowers the cost and technical hurdles.
- RNA interferences (RNAi): Used for gene expression knockdown through natural cellular mechanisms for viral detection. The big example here is Alnylam with 5 approved therapies and a number in clinical trials.
- Antisense Oligonucleotides (ASOs): Short single stranded RNA molecules that get delivered directly to the cell and target an existing mRNA. The big win here is Spinraza which is the first approved treatment for Spinal Muscular Atrophy (SMA) which previously didn't have a treatment. The Spinraza clinical trial (ENDEAR) was so effective that they deemed it unethical to continue it because the control arm wasn't receiving the treatment. Prior to Spinraza most patients would pass away prior to two years of age.