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

Virtual Cell Challenge: Toward a Turing test for the virtual cell

Virtual Cell Challenge: Toward a Turing test for the virtual cell

Yusuf H Roohani, Tony J Hua, Po-Yuan Tung, Lexi R Bounds, Feiqiao B Yu, Alexander Dobin, Noam Teyssier, Abhinav Adduri, Alden Woodrow, Brian S Plosky, Reshma Mehta, Benjamin Hsu, Jeremy Sullivan, Chiara Ricci-Tam, Nianzhen Li, Julia Kazaks, Luke A Gilbert, Silvana Konermann, Patrick D Hsu, Hani Goodarzi, Dave P Burke

CellJune 2025

Predicting cellular responses to perturbation across diverse contexts with STATE

Predicting cellular responses to perturbation across diverse contexts with STATE

Abhinav Adduri, Dhruv Gautam, Beatrice Bevilacqua, Alishba Imran, Rohan Shah, Mohsen Naghipourfar, Noam Teyssier, Rajesh Ilango, Sanjay Nagaraj, Chiara Ricci-Tam, Chris Carpenter, Vishvak Subramanyam, Aidan Winters, Mingze Dong, Sravya Tirukkovalur, Jeremy Sullivan, Brian Plosky, Basak Eraslan, Nicholas D Youngblut, Jure Leskovec, Luke A Gilbert, Silvana Konermann, Patrick D Hsu, Alexander Dobin, Dave P Burke, Hani Goodarzi, Hani Goodarzi, Yusuf Husein Roohani

Preprint: bioRxivJune 2025

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

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

BioRxivFebruary 2025

Sequence modeling and design from molecular to genome scale with Evo

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.

ScienceNovember 2024

Structural Mechanism of bridge RNA-guided recombination

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

NatureJune 2024

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

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 GeneticsJuly 2022

All Publications

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)

Christine Toha
Executive Assistant

Christine Toha

MSc Dance Science, Trinity Laban Conservatoire of Music & Dance

Andreas Puschnik
Associate Director of Discovery Biology and Functional Genomics‌

Andreas Puschnik

Ph.D., Microbiology and Immunology, Stanford University

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)

Januka Athukoralage
Senior Scientist

Januka Athukoralage

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

Gwanggyu Sun
Scientist

Gwanggyu Sun

Ph.D., Bioengineering, Stanford University

Nicholas Perry
Scientist

Nicholas Perry

PhD, Bioengineering, UC Berkeley

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

Juliana Martins
Graduate Student

Juliana Martins

UC Berkeley Molecular and Cell Biology PhD Program

Liam Bartie
Graduate Student

Liam Bartie

UC Berkeley Bioengineering PhD Program

Gabriel Gonzalez
Research Associate

Gabriel Gonzalez

BS, Biomedical Engineering, Columbia University

Lauren Lee
Research Associate

Lauren Lee

B.S., Biology, Santa Clara University

Alumni

Alison FantonProfluent
Dhruva Katrekar
Matthew DurrantSenior Fellow, FutureHouse
Michael HerschlScientist, NewLimit
Cyrus TauPhD Student at Harvard Medical School
Matthew NemethPhD Student at Columbia University
James PaiPhD Student, UC Berkeley-UCSF Bioengineering PhD Program
John McSpedonCo-Founder & CTO at Aequita Bioworks
Aditya JangidPhD Student, UC Berkeley-UCSF Bioengineering PhD Program
Shreeya AgrawalMedical Student at New 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., Ph.D.Physician & Assistant Professor at UC San Diego Health
Nick Hernandez, M.D.Resident Physician at UC San Diego Health
Aman SharmaResearch Assistant, Salk Institute

Out and about

Lab team photo 1
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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
Arc Institute Location