Paul Datlinger

Scientist. Inventor of CROP-seq & scifi-RNA-seq. AD @ Arc Institute & Virtual Cell Initiative | CAR T cells

[Paul Datlinger @PaulDatlinger]

The genome wizards at @arcinstitute strike again: bridge recombination in human cells. Congratulations to Patrick Hsu (@pdhsu), Silvana Konermann (@SKonermann) & team for pushing the boundaries of genome engineering.

[Patrick Hsu @pdhsu]

Today in @ScienceMagazine, we report a new DNA editing technology to seamlessly write massive changes into the right place in the human genome.

The reason gene editing hasn't transformed human health is that current gene editing technologies like CRISPR are very limited.

The problem with CRISPR is that it cuts up your DNA, and then hopes that unreliable cellular DNA repair will make the wanted edit. @geochurch famously called it genome vandalism. More precise versions of CRISPR only edit less than 100 bases - often only a single base. Therefore, it's not suited to make large changes safely.

However, most diseases are not the result of mutations in one location. Instead, their causes are spread all across the 3 billion base pairs in the genome.

We found bridge RNAs in bacterial “jumping genes” that allow us to make safe and arbitrary changes (insert, cut out, or flip) to every nucleotide within (up to) a 1 million bp sequence in your DNA.

In the paper, we show that we can correct the disease-causing DNA repeats that cause Friedreich's ataxia (which is a rare neurological disease). The same approach could be applied to Huntington’s and other repeat expansion disorders.
At @arcinstitute, we're working towards a full Turing machine for biology. Evo, our DNA foundation model, helps us design the optimal healthy DNA sequences. And Bridge recombination gives us the ability to seamlessly write these changes into the right place in the genome.
This work was a wonderful collaboration with my @arcinstitute cofounder @SKonermann and led by the indefatigable @ntperry13, alongside our amazing bridge editing team: @BartieLiam @dhruvakatrekar @Gabogonzalez515 @mgdurrant @james_jw_pai @AlisonFanton Juliana Martins Masa Hiraizumi @chiaroscurale @hnisimasu

[Patrick Hsu @pdhsu]

Today in @ScienceMagazine, we report a new DNA editing technology to seamlessly write massive changes into the right place in the human genome.

The reason gene editing hasn't transformed human health is that current gene editing technologies like CRISPR are very limited.

The problem with CRISPR is that it cuts up your DNA, and then hopes that unreliable cellular DNA repair will make the wanted edit. @geochurch famously called it genome vandalism. More precise versions of CRISPR only edit less than 100 bases - often only a single base. Therefore, it's not suited to make large changes safely.

However, most diseases are not the result of mutations in one location. Instead, their causes are spread all across the 3 billion base pairs in the genome.

We found bridge RNAs in bacterial “jumping genes” that allow us to make safe and arbitrary changes (insert, cut out, or flip) to every nucleotide within (up to) a 1 million bp sequence in your DNA.

In the paper, we show that we can correct the disease-causing DNA repeats that cause Friedreich's ataxia (which is a rare neurological disease). The same approach could be applied to Huntington’s and other repeat expansion disorders.
At @arcinstitute, we're working towards a full Turing machine for biology. Evo, our DNA foundation model, helps us design the optimal healthy DNA sequences. And Bridge recombination gives us the ability to seamlessly write these changes into the right place in the genome.
This work was a wonderful collaboration with my @arcinstitute cofounder @SKonermann and led by the indefatigable @ntperry13, alongside our amazing bridge editing team: @BartieLiam @dhruvakatrekar @Gabogonzalez515 @mgdurrant @james_jw_pai @AlisonFanton Juliana Martins Masa Hiraizumi @chiaroscurale @hnisimasu

[Paul Datlinger @PaulDatlinger]

@IdoAmitLab @Nature Thank you Ido, means a lot to me

[Paul Datlinger @PaulDatlinger]

#CELLFIE for CAR T screening, out in @Nature today—a new mRNA-based platform for screening primary cells. CAR + gRNA library are delivered by lentivirus, CRISPR modifiers as electroporated mRNA. That’s more flexible and effective than existing T cell screening methods. (1/7)

[Paul Datlinger @PaulDatlinger]

This is our proudest work yet—a blueprint for rationally designing next-generation cell therapies. Data and methods are fully open-source for academic use and licensable for translation. https://t.co/uaqwhcuiXM

[Paul Datlinger @PaulDatlinger]

Great teamwork: P Datlinger*✉️, E Pankevich*, C Arnold*, N Pranckevicius, J Lin, D Romanovskaia, M Schäfer, F Piras, AC Orts, A Nemc, P Biesaga, M Chan, T Neuwirth, A Artemov, W Li, S Ladstätter, T Krausgruber & C Bock✉️ (*first authors, ✉️correspondance).

[Paul Datlinger @PaulDatlinger]

CAR T cells showcase the enormous potential of cell therapies, but often fail due to lack of evolutionary optimization. Today in @Nature, we use #CELLFIE to engineer cell therapies at scale and share the largest resource of CRISPR screens in CAR T cells. https://t.co/uaqwhcuiXM

[Arc Institute @arcinstitute]

Today, Arc announced it is joining forces with @NVIDIAHealth to develop powerful computational tools that will help researchers everywhere explore and understand living systems in ways previously impossible. https://t.co/DuMOlg5pnr

[Patrick Hsu @pdhsu]

Excited to partner with @Nvidia and @NVIDIAHealth to scale the potential of AI models to design, predict, and understand biology. Our goal is to discover emergent properties of life, similar to those found in language, videos, and robotics

https://t.co/O9hvmR0m49

[Paul Datlinger @PaulDatlinger]

Interested to screen T cells for Arc’s Virtual Cell Initiative and explore AI virtual cells in cancer immunotherapy? I’m looking for a talented Scientist to join my team at the @arcinstitute in Palo Alto, California. Apply here! https://t.co/tqEN7Jxeqy

[Paul Datlinger @PaulDatlinger]

@yusufroohani @arcinstitute @NeurIPSConf Congratulations, @yusufroohani & all co-authors. I really enjoyed this perspective and in particular the concept of virtual instruments (VIs). You have really great ideas, and I'm super excited to work on this together.

[Yusuf Roohani @yusufroohani]

Enjoyed writing this perspective on an AI-powered virtual cell with amazing collaborators

But it’s been even more fun actually building it! 🔧

Check out open positions @ArcInstitute or find us @NeurIPSConf

[William Allen @weallen1]

In collaboration with Reuben Saunders, @JswLab, and Xiaowei Zhuang, we are very excited to release Perturb-Multi: a platform for pooled multimodal genetic screens in intact mammalian tissue.

Check it out!
https://t.co/iJ8hi3ddz4

[Arc Institute @arcinstitute]

🧬Evo, the first foundation model trained at scale on DNA, is a Rosetta Stone for biology.

DNA, RNA, and proteins are the fundamental molecules of life—and cracking the code of their complex language is an ongoing grand challenge.

🔬Today in @ScienceMagazine, the labs of Arc Innovation Investigator @BrianHie and Arc Co-Founder @pdhsu explain how Evo captures two fundamental aspects of biology: the multi-modality of the central dogma and the multi-scale nature of evolution. Evo excels at prediction and generation tasks across all of these molecules and their interactions.

An exciting example of what Evo can do: the team used it to design a totally new CRISPR system, including a guide RNA that makes Cas9 cut even better. Evo can also design DNA sequences over one million base pairs in length, reaching the size of many real genomes.

🧠Check out the paper now in Science: https://t.co/RsjE674qnW