Nature Search

Custom CRISPR–Cas9 PAM variants via scalable engineering and machine learning

Combined high-throughput protein engineering with machine learning to curate libraries of CRISPR genome-editing enzymes with distinct genome targeting properties is described.

Rachel A. Silverstein
Nahye Kim
Benjamin P. Kleinstiver
Research22 Apr 2025
Nature

P: 1-12
Publisher Correction: R-loop formation and conformational activation mechanisms of Cas9

Martin Pacesa
Luuk Loeff
Martin Jinek
Amendments and CorrectionsOpen Access30 Oct 2023
Nature

Volume: 623, P: E10
Computational design of soluble and functional membrane protein analogues

A deep learning approach enables accurate computational design of soluble and functional analogues of membrane proteins, expanding the soluble protein fold space and facilitating new approaches to drug screening and design.

Casper A. Goverde
Martin Pacesa
Bruno E. Correia
ResearchOpen Access19 Jun 2024
Nature

Volume: 631, P: 449-458
Targeting protein–ligand neosurfaces with a generalizable deep learning tool

A computational deep learning approach is used to design synthetic proteins that target the neosurfaces formed by protein–ligand interactions, with applications in the development of new therapeutic modalities such as molecular glues or cell-based therapies.

Anthony Marchand
Stephen Buckley
Bruno E. Correia
ResearchOpen Access15 Jan 2025
Nature

Volume: 639, P: 522-531
PAM-flexible genome editing with an engineered chimeric Cas9

CRISPR enzymes require a defined protospacer adjacent motif (PAM) which can be limiting for editing applications. Here the authors recombine the PAM-interacting ___domain of SpRY with the N-terminus of Sc + + to generate a chimeric enzyme with highly flexible PAM preference: SpRYc.

Lin Zhao
Sabrina R. T. Koseki
Pranam Chatterjee
ResearchOpen Access04 Oct 2023
Nature Communications

Volume: 14, P: 1-8
Principles of target DNA cleavage and the role of Mg²⁺ in the catalysis of CRISPR–Cas9

A detailed understanding of the catalytic target DNA cleavage mechanism by CRISPR–Cas9 has been lacking. Now the key modulating role of Mg²⁺ in the conformational activation of Cas9 and the influence of active site residues on the protonation state of catalytic H840 are demonstrated, ultimately unravelling the catalytic mechanism.

Łukasz Nierzwicki
Kyle W. East
Giulia Palermo
Research06 Oct 2022
Nature Catalysis

Volume: 5, P: 912-922
R-loop formation and conformational activation mechanisms of Cas9

Cryo-electron microscopy structures of Streptococcus pyogenes Cas9 in multiple DNA-bound states provide insights on the mechanism of Cas9 activation by target DNA.

Martin Pacesa
Luuk Loeff
Martin Jinek
ResearchOpen Access24 Aug 2022
Nature

Volume: 609, P: 191-196
In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels

Base editors are effective and safe for cholesterol reduction in non-human primates.

Tanja Rothgangl
Melissa K. Dennis
Gerald Schwank
ResearchOpen Access19 May 2021
Nature Biotechnology

Volume: 39, P: 949-957
De novo design of protein interactions with learned surface fingerprints

A surface-centric approach captures the physical and chemical determinants of molecular recognition, enabling the de novo design of protein interactions and of artificial proteins with function.

Pablo Gainza
Sarah Wehrle
Bruno E. Correia
ResearchOpen Access26 Apr 2023
Nature

Volume: 617, P: 176-184
Target site selection and remodelling by type V CRISPR-transposon systems

Structural studies on Scytonema hofmanni CRISPR-associated transposon protein complexes indicate a mechanism for RNA-guided DNA transposition involving Cas12k, TnsC and TnsB.

Irma Querques
Michael Schmitz
Martin Jinek
Research10 Nov 2021
Nature

Volume: 599, P: 497-502
Continuous directed evolution of a compact CjCas9 variant with broad PAM compatibility

Through directed evolution, the PAM compatibility of the compact Cas9 variant CjCas9 was increased. Evolved CjCas9 shows higher nuclease activity at canonical and non-canonical sites and enables robust in vivo gene editing from single AAV vectors.

Lukas Schmidheini
Nicolas Mathis
Gerald Schwank
Research21 Sept 2023
Nature Chemical Biology

Volume: 20, P: 333-343

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Custom CRISPR–Cas9 PAM variants via scalable engineering and machine learning

Publisher Correction: R-loop formation and conformational activation mechanisms of Cas9

Computational design of soluble and functional membrane protein analogues

Targeting protein–ligand neosurfaces with a generalizable deep learning tool

PAM-flexible genome editing with an engineered chimeric Cas9

Principles of target DNA cleavage and the role of Mg²⁺ in the catalysis of CRISPR–Cas9

R-loop formation and conformational activation mechanisms of Cas9

In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels

De novo design of protein interactions with learned surface fingerprints

Target site selection and remodelling by type V CRISPR-transposon systems

Continuous directed evolution of a compact CjCas9 variant with broad PAM compatibility

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