David R. Liu

Professor at Harvard and the Broad Institute. Our lab integrates chemistry & evolution to illuminate biology & enable new therapeutics. IG/Threads: @davidrliu1

[David R. Liu @davidrliu]

Today in @Nature we report how AI-guided redesign enhances protein evolution. Integrating ProteinMPNN sequence design with autonomous laboratory evolution, we establish a workflow to engineer enzymes with improved properties over those evolved from natural proteins. Redesigned starting points consistently evolve an expanded fitness landscape, reaching new function with higher activity, specificity, and stability than their natural counterparts.
https://t.co/pNlw6z1zvU
1/14

[David R. Liu @davidrliu]

This work was led by @NicholasKrasnow, with key contributions from Joy Xu, @emilyzhang326, Gandhar Mahadeshwar, @Allentaoyz, Julia McCreary, Colin Hemez, Logan Brown, and Wei Jiang. Congratulations to the authors!
The paper is available on the @Nature website: https://t.co/1x8YoBRABa
PDF of SI: https://t.co/vckgy1rf7Y
14/14

[David R. Liu @davidrliu]

Today in @Nature we report how AI-guided redesign enhances protein evolution. Integrating ProteinMPNN sequence design with autonomous laboratory evolution, we establish a workflow to engineer enzymes with improved properties over those evolved from natural proteins. Redesigned starting points consistently evolve an expanded fitness landscape, reaching new function with higher activity, specificity, and stability than their natural counterparts.
https://t.co/pNlw6z1zvU
1/14

[David R. Liu @davidrliu]

Finally, we applied these findings to evolve proteases that specifically cleave the disease-relevant protein ataxin-2. Redesign-evolved proteases had higher expression, stability, and ataxin-2 cleavage rates than those evolved from wild-type. Importantly, the best redesign-evolved variants eliminated off-target cleavage of the native substrate, achieving >79-fold selected specificity than the top wild-type evolved proteases. Once again, mutations that confer high activity and specificity in the redesign background result in a dead enzyme when grafted into the wild-type protein, highlighting that redesign was essential to evolve these superior genotypes.
13/14

[David R. Liu @davidrliu]

Experts in gene editing, n=1 medicine development, in vivo delivery, rare diseases, and cell & animal models of genetic disorders have founded the Center for Therapeutic Genetics (CTG), a non-profit effort involving @broadinstitute @BostonChildrens @jacksonlab, as well as others from industry, academia, and patient advocacy organizations, to bring the promise of programmable medicines including base and prime editors to patients suffering from rare genetic diseases. This article from @ginakolata @nytimes frames the compelling need: https://t.co/OyrYCZtWIk

Official announcement: https://t.co/MwJCUarQnX

[Broad Institute @broadinstitute]

We're thrilled to announce the Center for Therapeutic Genetics (CTG) — a new collaboration between Broad, Boston Children’s Hospital, and The Jackson Laboratory to develop genetic medicines for rare and ultra-rare diseases. https://t.co/fnkbAQwJE4 (1/3)

[Prime Medicine @PrimeMedicine]

Proud to contribute to Broad Institute-led PERC Gene Editing Platform, selected to receive up to $34.5M from @ARPA_H THRIVE program. Together we're working to advance gene-editing approaches for rare pediatric epilepsies, including Dravet syndrome & AHC. https://t.co/IqaCM9ebTm

[Broad Institute @broadinstitute]

We're thrilled to announce that a Broad-led consortium of 12 organizations has been selected to receive funding from @ARPA_H under its THRIVE program to launch the Pediatric Epilepsies and Rare CNS (PERC) Gene Editing Platform. https://t.co/gTZ99b9gl7 (1/5)

[Broad Institute @broadinstitute]

Prime editing has continuously improved since @davidrliu's lab introduced it in 2019. 3 new studies from his lab advance prime editing systems, addressing key bottlenecks by increasing the efficiency and improving its potency when delivered into the body. https://t.co/r9qYb2eaXb

[Yair Einhorn @yaireinhorn]

1/🚨WOW! Prime Medicine just announced that the U.S FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to PM359 - $PRME leading autologous stem Cell Therapy for the treatment of p47phox-deficient Chronic Granulomatous Disease (CGD). RMAT designation is not only a super important milestone - which was granted to Prime Medicine based on PM359’s previous promising Phase 1/2 clinical data 🧵👇, but it will also provide the company with significant benefits such as an intensive FDA guidance and an expedited review through the program’s development. $XBI