Jamie Rintoul

PhD candidate @UCL, working on better CAR T cells

[Jamie Rintoul @JamieRintoul2]

@pdhsu I’d been hoping to see more RIPTAC-style molecules with target:semi-arbitrary tissue-specific protein pairs. Where ligands are inert + pharmacology is driven by mislocalisation/steric hindrance/degradation. Aware of a group in Dundee mining for CNS-specific effectors in this vein

[Jonas Koeppel @JonasKoeppel]

1/n What fraction of the human genome is essential for cellular viability?

Excited to share our preprint that explores this question by combining an unusual CRISPR system, phage promoters, and thousands of deletion launchpads.

@sudpinglay @JShendure

https://t.co/rTO1MyFv3q

[Chordoma Foundation Labs @CFLabsResearch]

Much debate right now about the binding affinity prediction abilities of AI models. For anyone interested in validating model predictions experimentally we can provide that for free for the oncology target TBXT. Plus we’re offering $500k in prizes for submicromolar binders: https://t.co/uJBHTcMy3e

[Jamie Rintoul @JamieRintoul2]

Exact same prompt to ChatGPT btw...
(I didn't crop it)

[Jamie Rintoul @JamieRintoul2]

Using nanobanana2 to illustrate my sequencing analysis pipeline- one shot from a simple, detailed description. pretty insane vs SOTA 1 week ago…

Not flashy “AI for science”, but less time tediously making slides means more time thinking/doing

[Roth_Lab @Roth_Lab]

Excited to present the first major work after starting our lab at Stanford and the Arc this year: CRISPR-All, a unified genetic perturbation language for programming any major type of genetic perturbation simultaneously, in any combination, at genome scale, in human cells.

[Pranam Chatterjee @pranamanam]

Real-world validation time for one of our lab's favorite new therapeutic peptide design algorithms: MOG-DFM! 💥

As a reminder, our multi-objective-guided discrete flow matching (MOG-DFM) algorithm, developed by my brilliant PhD student @TongChen321, learns Pareto-efficient transport in discrete sequence space, re-weighting token velocities through rank-directional scoring and adaptive hypercone filtering to balance competing properties like affinity, solubility, half-life, hemolysis, and non-fouling. ⚖️ Best of all, guidance happens at inference time using black boxed predictors! ⬛

@adaptvbio tested 24 of our MOG-DFM-designed peptides, and 6 bound cleanly to their target, FcRn, a key autoimmune target that recycles IgG. ♻️ We're synthesizing these 6 now in my lab @Penn and doing property testing before moving into antagonism assays and autoimmune animal studies! 🧪 ➡️ 🧫 ➡️ 🐁

It’s so gratifying to see designs from theory to bench so quickly. We're super grateful to @julian_englert, @CotetTudor, and the @adaptvbio team for their collaboration and spotlight! I highly recommend working with them if you're doing anything binder design -- it was so fun! 🙌

Also, if you want to use MOG-DFM for your targets, check out our paper (which was awarded a Spotlight at the ICML @genbio_workshop) and model on @huggingface:

📜: https://t.co/KcV1aU7PDD
🤗: https://t.co/cHAdy6xfZz

[Jing Liang 🇺🇦 @AppleHelix]

Honestly, I am surprised at the premium of these **preclinical** in vivo CAR-T deals. I suspect it will be commoditize relatively shortly.

[Jamie Rintoul @JamieRintoul2]

Would love to hear people's thoughts. Highly recommend reading here: https://t.co/rr8NjKMV5j

(Also thanks to @drughunter_com for flagging the paper!)

[Jamie Rintoul @JamieRintoul2]

Amazing paper from April - CD36, a multi-functional fatty acid transporter, mediates cell uptake of PROTACs + other large "small" molecules via endocytosis. So many interesting implications for dev. of heterobifunctionals more broadly! I'm a naive biologist so perhaps... 1/n

[Jamie Rintoul @JamieRintoul2]

CD36 loss as a new mechanism of resistance/relapse + patient stratification criterion? (Existing Arvinas data might answer)
An IP land grab of better-in-class PROTACs bearing CD36-engagement in mind? (How many Chinese cos already have large libraries of ARV-xxx derivatives?) 5/n

[Kieran Didi @DidiKieran]

Check out La-Proteina, our new model for all-atom structure generation at scale! Was a very fun project to work on with @tomasgeffner and the rest of the team. Two things I am particularly excited about in 🧵 1/n

[Alissa Hummer @AlissaHummer]

Our work exploring the ability of and requirements for ML to predict the effects of mutations on antibody–antigen binding affinity (ΔΔG) is out now in @NatComputSci!

[Kyle G Daniels @ScienceKyle]

🚨 New Preprint 🚨
A continuous landscape of signaling encodes a corresponding landscape of CAR T cell phenotype

How can we tune JAK/STAT signaling to create better immune cell therapies?

https://t.co/ejW8rpxzmW

[Anand Muthusamy @mu_anand]

Biology is blessed.
@owl_posting we're on some kind of mind meld because was literally now going through decks and making this to cheer you up lol

[Jake P. Taylor-King @wildtypehuman]

"To be clear, no one has proposed using ROCK inhibitors to treat dry AMD in the literature before, as far as we can find..."

It's so unprecedented, there's even a review article...
https://t.co/oHMgZcyLSi

[Jamie Rintoul @JamieRintoul2]

@oxytheca Thanks, Anna!

[Jamie Rintoul @JamieRintoul2]

Interesting read from @SimonDBarnett & @oxytheca – totally agree that early thinking around product profile and market access is essential, but I feel the article slightly misrepresents what a TPP actually is (at least canonically) and why it’s useful. Some thoughts below:
1/7

[Simon Barnett @SimonDBarnett]

📰 New Original Essay ~ on the increasing relevance of target product profiles (TPPs) in biotech

@oxytheca and I spoke with commercial, market, and R&D teams across large pharma to understand TPP utilization in modern product strategy.

Full essay linked at end! 🔗