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Launch HN: BlankBio (YC S25) – Making RNA Programmable

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Re: Launch HN: BlankBio (YC S25) – Making RNA Programmable

#21
post #14

Earlier quoted context omitted.

> ground truth Hey yes, the ground truth for our evaluations is measured experimental data. Our models are benchmarked using mRNABench, which aggregates results from high-throughput wet lab experiments. Our goal, however, is to move beyond predicting existing experimental outcomes. We intend to design novel sequences and validate their function in our own lab. At that stage, the functional success of the RNA we desig…

> mRNABench Just curious, in other areas of ML, I think it's widely acknowledged that benchmarks have pretty limited real world value, just end up getting saturated, and (my view) are all pretty correlated, regardless of their ostensible speciality and don't really tell you that much. Do you think mRNABench is different, or where do you see the limitations? Do you imagine this or any benchmark will be useful for anyt…

Here is the link for benchmarks and their utility: https://youtu.be/JdT78t1Offo?t=1444

"We have internal benchmarks. Yeah. But we don't we don't publish them."

"we have internal benchmarks that the team focuses on and improving and then we also have a bunch of tasks like I think that accelerating our own engineers is like a top top priority for us"

The equivalent for us would be to ultimate looking to improve experimental results. Benchmarks are a good intermediate point but not the ultimate goal

Re: Launch HN: BlankBio (YC S25) – Making RNA Programmable

#22

Literally the stuff of nightmares. Why are we doing this? > As compilers freed programmers from low-level details, we're building the abstraction layer for RNA. That’s all fun and games when it’s literally fun and games. When it’s mRNA injected into living beings it’s the stuff of nightmares. Will technologists ever _ever_ stop and think for a second?

I don't expect the new mRNA to be injected in humans directly. I guess it will be try in mice, then in other animals, then in a few humans, then in a bigger group, and then available to the general public. (Or something like that, I don't remember the details, IANAMD.)

It's the usual process for all new medicines. We already had a lot of bad cases with other potential medicines, so all new candidates must pass a lot of tests.

Re: Launch HN: BlankBio (YC S25) – Making RNA Programmable

#23
Fascinating platform. I'm fairly new in my bio education but are you effectively finding sequences on NIH and then intelligently chaining them together?

I had some fun one evening asking Claude how I could string together sequences for an imaginary therapeutic and it gave me enough to put into alphafold and get a render :) (Worst therapeutic ever: deliver mRNA into macrophages to target those pesky bacteria who happily just choose to reside there)

Also: How do you plan to navigate the unfortunate part of our country trying to write mRNA out of the American vocabulary?

Re: Launch HN: BlankBio (YC S25) – Making RNA Programmable

#24

Earlier quoted context omitted.

This is a really interesting direction. There is this big field of Cell Free (cfRNA) cancer detection. We talked to a few people in the field and think that embedding sequences for this direction could be really valuable. One challenge here is that it's hard to set up evaluation tasks since the public data is scarce

Maybe we can crowd source data. My platform, currently in beta, has ai assistants for compute infrastructure and biology and will soon let people to do self serve research on their own omics data using models like yours. So there could be a monetization path too if enough people start looking their own cell data (which they might once they fully understand the risks of engineered pathogens, and certainly will when th…

That would be really cool. Navigating SRA and mining out reasonable $ relevant tasks is a huge bottleneck.

I find it takes a large amount of effort to parse what the authors are doing, whether the data is high quality, and how to pre-process it in a way that makes sense for the task at hand.

Would love to chat more about how you're thinking of evaluating quality of these agents.

Re: Launch HN: BlankBio (YC S25) – Making RNA Programmable

#25

Fascinating platform. I'm fairly new in my bio education but are you effectively finding sequences on NIH and then intelligently chaining them together? I had some fun one evening asking Claude how I could string together sequences for an imaginary therapeutic and it gave me enough to put into alphafold and get a render :) (Worst therapeutic ever: deliver mRNA into macrophages to target those pesky bacteria who happi…

> finding sequences on NIH

Almost! Yes most of the data is on NIH sub-institutes. For us we take most of the data from NCBI and intelligently pair it together. The training objective of our model takes pairs of sequences (thus the Joint Embedding Architecture) and trains the model to recognize that they are semantically similar but differ in appearance. This is conceptually similar to a lot of the contrastive learning literature from computer vision.

Sounds like a fun side project :)

There are some great tools out there for putting together plasmids for gene therapies where you can plug in different "elements". Promoters UTRs payloads - check out SnapGene I believe they have a free version.

I personally am hopeful that the political headwinds will blow over. When it comes to cancer vaccines it's one of the most exciting new modalities for treating cancer.

1 in 2 Americans are going to get cancer in their lifetime so no matter political affiliation, the need for health will ultimately drive people to invest in the modality.

Re: Launch HN: BlankBio (YC S25) – Making RNA Programmable

#26

The other day I paired an article on pyroptosis caused by marine spongiibacter exopolysaccharide and an mRNA Cancer vaccine article. I started to just forward the article on bacterially-induced pyroptosis to the cancer vaccine researchers but stopped to ask an LLM whether the approaches shared common pathways or mechanisms of action and - fish my wish - they are somehow similar and I had asked a very important questi…

Can EPS3.9 cause pyroptosis cause IFN-I cause epitope spreading for cancer treatment? Re: "Sensitization of tumours to immunotherapy by boosting early type-I interferon responses enables epitope spreading" (2025) https://www.nature.com/articles/s41551-025-01380-1 How is this relevant to mRNA vaccines?: "Ocean Sugar Makes Cancer Cells Explode" (2025) https://scitechdaily.com/ocean-sugar-makes-cancer-cells-expl... ...…

This is really interesting - I'm going to be honest I'm not an immunologist so this is my (LLM assisted) understanding of your comment:

The immune system recognizes a sugar as a PAMP, or Pathogen-Associated Molecular Pattern, which is a signature of a potential microbial threat.

This initiates pyroptosis an inflammatory form of programmed cell death causing the cell to burst. This rupture releases tumor antigens and DAMPs (Damage-Associated Molecular Patterns), which are "danger signals" from the dying cell

The release of DAMPs shifts the Tumor Microenvironment (TME) from an immunologically "cold" to a "hot" state, promoting a potent Type I Interferon (IFN-I) response.

The release of DAMPs shifts the Tumor Microenvironment (TME) from an immunologically "cold" to a "hot" state, promoting a potent Type I Interferon (IFN-I) response.

This response recruits Antigen Presenting Cells (APCs), which engulf the newly released tumor antigens.

---

mRNA vaccines are somewhat of a parallel approach where the antigen selection and delivery happens manually. An mRNA vaccine delivers the encoding sequence for specific tumor antigens to drive production and presentation, training the immune system. One of the big challenges of this space is optimal antigen selection from the patient's tumor.

One thing I'm not fully clear on is why only tumor cell react to PAMP instead of healthy cells. Could be a promising approach but molecular biology is pretty tricky and the devil is always in the details.

Re: Launch HN: BlankBio (YC S25) – Making RNA Programmable

#27

Earlier quoted context omitted.

Can EPS3.9 cause pyroptosis cause IFN-I cause epitope spreading for cancer treatment? Re: "Sensitization of tumours to immunotherapy by boosting early type-I interferon responses enables epitope spreading" (2025) https://www.nature.com/articles/s41551-025-01380-1 How is this relevant to mRNA vaccines?: "Ocean Sugar Makes Cancer Cells Explode" (2025) https://scitechdaily.com/ocean-sugar-makes-cancer-cells-expl... ...…

This is really interesting - I'm going to be honest I'm not an immunologist so this is my (LLM assisted) understanding of your comment: The immune system recognizes a sugar as a PAMP, or Pathogen-Associated Molecular Pattern, which is a signature of a potential microbial threat. This initiates pyroptosis an inflammatory form of programmed cell death causing the cell to burst. This rupture releases tumor antigens and…

> "why only tumor cell react to PAMP instead of healthy cells"

I am not a scientist, but I believe that "normal" cells do not seek long-chain alien sugars like those produced by ocean bacteria. Conversely, "cancerous" cells may find these uncommon sugars appealing, and they consume sugar eagerly (Warburg effect).

After the alien sugars are metabolized, fragments migrate to the cell membrane and might be recognized by the immune system as foreign.

The fact that large molecules trigger Pyroptosis may be helpful.

Re: Launch HN: BlankBio (YC S25) – Making RNA Programmable

#28

I am totally onboard with the premise (as a TechBio-adjacent person), and some of the approaches you're taking (focused domain-specific models like Orthrus, rather than massive foundation models like Evo2). I'm curious about what your strategy is for data collection to fuel improved algorithmic design. Are you building out experimental capacity to generate datasets in house, or is that largely farmed out to partners?

We think that Orthrus can be applied in a bunch of ways to non-coding and coding RNA sequences but it's definitely fair we're a bit more focused on RNA sequences currently instead of non-coding parts of the genome like promoters and intergenic sequences. For the data - Orthrus is trained on non experimentally collected data so our pre-training dataset is large by biological standards. It adds up to about 45 million u…

Thanks for the response! This is very cool and sounds like a reasonable plan. Best of luck!

Re: Launch HN: BlankBio (YC S25) – Making RNA Programmable

#29

Fun to see talk of "a compiler for DNA"---I've been hoping for that for a long time. I have to admit, at a _glance_ this feels like a promising idea with few results and lots of marketing. I'll try to be clear about my confusion, feel free to explain if I'm off base. - There's not a lot of talk of your "ground truth" for evaluations. Are you using mRNABench? - Has you mRNABench paper been peer reviewed? You linked a…

> ground truth Hey yes, the ground truth for our evaluations is measured experimental data. Our models are benchmarked using mRNABench, which aggregates results from high-throughput wet lab experiments. Our goal, however, is to move beyond predicting existing experimental outcomes. We intend to design novel sequences and validate their function in our own lab. At that stage, the functional success of the RNA we desig…

Thank you for writing out these answers! Your patience was noticed and appreciated.

It feels like things are further ahead in synthetic biology than I realized and that so so so exciting!

(yes, I meant "out of distribution"---but in today's day 'n age typos are proof of human creation :p )

Re: Launch HN: BlankBio (YC S25) – Making RNA Programmable

#30

Literally the stuff of nightmares. Why are we doing this? > As compilers freed programmers from low-level details, we're building the abstraction layer for RNA. That’s all fun and games when it’s literally fun and games. When it’s mRNA injected into living beings it’s the stuff of nightmares. Will technologists ever _ever_ stop and think for a second?

mRNA is a natural molecule produced by every living organism. All it does it cause a protein to be made. Where's the nightmare?
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