Generative genomics for biological design

We are a lab of inventors working at the intersection of biology, engineering, and AI to develop technologies for biological programming
Hsu Lab

Research Focus

1

BIOLOGICAL PROGRAMMING

We are interested in programming biology at multiple levels of scale. Our contributions in this area include the early development of CRISPR-Cas9 for human genome editing, the discovery and development of CRISPR-Cas13d for transcriptome engineering, and the discovery and development of multiple classes of recombinases (bridge RNA-guided recombinases and new large serine recombinases) for large-scale DNA rearrangement and genome design. We are interested in applying these tools to manipulate higher-levels of biological organization at the tissue and physiological levels.

screens

HUMAN SYNTHETIC BIOLOGY

We aim to push the boundaries of synthetic biology, which we define broadly as anything that doesn‘t happen naturally. First, we think backwards from the desired application, such as a major unmet therapeutic need, and develop platform solutions that enable new kinds of synthetic manipulations. Recent areas of interest include cell type-specific control of biological perturbations, turning the dial on epigenetic memory, and manipulation of RNA splicing for writing RNAs directly into the endogenous transcriptome. We are also thinking about synthetic hormones, rational nutrition, and interoception.

genome

MERGING BIOLOGY AND AI

The genome is a sequence that transmits the results of evolution across generations of life and completely encodes the DNA, RNA, and proteins that orchestrate the function of a whole organism. Advances in machine learning combined with massive genomic datasets could enable a biological foundation model that learns the intrinsic logic of whole genomes. Further integration of such a model with environmental inputs would be the first steps towards simulating a virtual cell. We are interested in prediction tasks that reveal fundamental biological mechanisms as well as generation tasks that enable genome-scale biological design in living cells.

Publications

Genome modeling and design across all domains of life with Evo 2

Garyk Brixi, Matthew G. Durrant, Jerome Ku, Michael Poli, Greg Brockman, Daniel Chang, Gabriel A. Gonzalez, Samuel H. King, David B. Li, Aditi T. Merchant, Mohsen Naghipourfar, Eric Nguyen, Chiara Ricci-Tam, David W. Romero, Gwanggyu Sun, Ali Taghibakshi, Anton Vorontsov, Brandon Yang, Myra Deng, Liv Gorton, Nam Nguyen, Nicholas K. Wang, Etowah Adams, Stephen A. Baccus, Steven Dillmann, Stefano Ermon, Daniel Guo, Rajesh Ilango, Ken Janik, Amy X. Lu, Reshma Mehta, Mohammad R.K. Mofrad, Madelena Y. Ng, Jaspreet Pannu, Christopher Ré, Jonathan C. Schmok, John St. John, Jeremy Sullivan, Kevin Zhu, Greg Zynda, Daniel Balsam, Patrick Collison, Anthony B. Costa, Tina Hernandez-Boussard, Eric Ho, Ming-Yu Liu, Thomas McGrath, Kimberly Powell, Dave P. Burke, Hani Goodarzi, Patrick D. Hsu, Brian L. Hie

BioRxiv • February 2025

Sequence modeling and design from molecular to genome scale with Evo

Eric Nguyen, Michael Poli, Matthew G. Durrant, Brian Kang, Dhruva Katrekar, David B. Li, Liam J. Bartie, Armin W. Thomas, Samuel H. King, Garyk Brixi, Jeremy Sullivan, Madelena Y. Ng, Ashley Lewis, Aaron Lou, Stefano Ermon, Stephen A. Baccus, Tina Hernandez-Boussard, Christopher Ré, Patrick D. Hsu and Brian L. Hie.

Science • November 2024

Structural Mechanism of bridge RNA-guided recombination

Masahiro Hiraizumi*, Nicholas T. Perry, Matthew G. Durrant, Teppei Soma, Naoto Nagahata, Sae Okazaki, Januka S. Athukoralage, Yukari Isayama, James J. Pai, April Pawluk, Silvana Konermann, Keitaro Yamashita, Patrick D. Hsu, Hiroshi Nishimasu

Nature • June 2024

Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection

Scott B. Biering, Sylvia A. Sarnik, Eleanor Wang, James R. Zengel, Sarah R. Leist, Alexandra Schäfer, Varun Sathyan, Padraig Hawkins, Kenichi Okuda, Cyrus Tau, Aditya R. Jangid, Connor V. Duffy, Jin Wei, Rodney C. Gilmore, Mia Madel Alfajaro, Madison S. Strine, Xammy Nguyenla, Erik Van Dis, Carmelle Catamura, Livia H. Yamashiro, Julia A. Belk, Adam Begeman, Jessica C. Stark, D. Judy Shon, Douglas M. Fox, Shahrzad Ezzatpour, Emily Huang, Nico Olegario, Arjun Rustagi, Allison S. Volmer, Alessandra Livraghi-Butrico, Eddie Wehri, Richard R. Behringer, Dong-Joo Cheon, Julia Schaletzky, Hector C. Aguilar, Andreas S. Puschnik, Brian Button, Benjamin A. Pinsky, Catherine A. Blish, Ralph S. Baric, Wanda K. O’Neal, Carolyn R. Bertozzi, Craig B. Wilen, Richard C. Boucher, Jan E. Carette, Sarah A. Stanley, Eva Harris, Silvana Konermann & Patrick D. Hsu

Nature Genetics • July 2022

All Publications

News

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Team

Patrick Hsu
COFOUNDER AND CORE INVESTIGATOR

Patrick Hsu

Patrick Hsu is Co-Founder of the Arc Institute and Assistant Professor of Bioengineering and Deb Faculty Fellow at the University of California, Berkeley. The Hsu lab works at the intersection of biology, engineering, and AI to develop technologies for biological programming and design. Patrick received A.M. and Ph.D. degrees from Harvard University and the Broad Institute, where he was an early pioneer of CRISPR-Cas9 technologies for genome editing. His research has been recognized by MIT Technology Review's Innovators Under 35, the Amgen Young Investigator Award, Forbes' 30 Under 30, the NIH Early Independence Award, and the Rainwater Prize for Innovative Early Career Scientist.

Current Members

Kiki Chu
Lab Manager

Kiki Chu

Massachusetts General Hospital/Harvard Medical School (Postdoc) & University of Wisconsin-Madison (PhD in Biochemistry)

Alessandra Sclip
Senior Scientist

Alessandra Sclip

Stanford (Postdoc) & Open University of London (PhD)

Jay Salvi
Senior Scientist

Jay Salvi

Stanford University (Postdoc) & University of Toronto (PhD in Pathobiology)

Matthew Durrant
Senior Scientist

Matthew Durrant

UC Berkeley (Postdoc) & Stanford University (PhD in Genetics)

Januka Athukoralage
Senior Scientist

Januka Athukoralage

UCSF (Postdoc) & University of St Andrews (PhD in Biochemistry)

Dhruva Katrekar
Senior Scientist

Dhruva Katrekar

PhD, Bioengineering, UC San Diego

Chad Moon
Postdoctoral Researcher

Chad Moon

Seoul National University (PhD in Biophysics)

Vincent Tran
Postdoctoral Researcher

Vincent Tran

PhD, Chemistry, UC Berkeley

Sita Chandrasekaran
Postdoctoral Researcher

Sita Chandrasekaran

PhD, Bioengineering, UC Berkeley

Alison Fanton
Scientist

Alison Fanton

PhD, Bioengineering, UC Berkeley

Nicholas Perry
Graduate Student

Nicholas Perry

UC Berkeley-UCSF Joint PhD Program in Bioengineering

Michael Herschl
Graduate Student

Michael Herschl

UC Berkeley-UCSF Joint PhD Program in Bioengineering

Juliana Martins
Graduate Student

Juliana Martins

UC Berkeley Molecular and Cell Biology PhD Program

Liam Bartie
Research Associate

Liam Bartie

B.S.E Chemical and Biomolecular Engineering, University of Pennsylvania

Gabriel Gonzalez
Research Associate

Gabriel Gonzalez

BS, Biomedical Engineering, Columbia University

Christine Toha
Executive Assistant

Christine Toha

MSc Dance Science, Trinity Laban Conservatoire of Music & Dance

Gwanggyu Sun
Scientist

Gwanggyu Sun

Ph.D., Bioengineering, Stanford University

Lauren Lee
Research Associate

Lauren Lee

B.S., Biology, Santa Clara University

Alumni

John McSpedonMachine Learning Engineer
Aditya JangidPhD Student, UC Berkeley-UCSF Bioengineering PhD Program
Shreeya AgrawalNew York Medical College
Eleanor WangPhD Student at UC Berkeley
Sylvia SarnikPhD Student at UC Boulder
Edward HanUC Berkeley, Class of 2021
Varun SathyanSoftware Engineer at Palantir
Yuxuan LanUC Berkeley, M. Eng, Class of 2020
Peter LotfyPhD Student at Harvard
Kian FaiziPhD Student at Caltech
Jennifer OkiData Scientist at Metagenomi
Nick Brideau, Ph.D.Senior Scientist at Debut Biotech
Tom Alsaigh, M.D.Resident Physician at Scripps Health
Nick HernandezMedical Student at Tufts University
Aman SharmaResearch Assistant, Salk Institute
Cyrus Tau
Matthew Nemeth

Out and about

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Contact Us

Some of the problems we are thinking about include RNA-guided genome design (e.g. with our recently discovered bridge recombinases), AI foundation models for generative DNA and protein design, and directly programming our physiology with soluble factors and synthetic hormones (biological programming is much more powerful than editing individual genetic loci).

Please visit Arc Institute’s Open Jobs for current posted positions or reach out to Patrick if you’re interested in joining us!

Address

Arc Institute
3181 Porter Dr
Palo Alto, CA 94304
info@arcinstitute.org
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