Bio

David Cox is an Assistant Professor of Genetics and by courtesy of Medicine (Hematology) at Stanford University and Principal Investigator of the Cox Lab (coxlab.bio), which is opening in July 2025. He is also a ChEM-H Institute Scholar and Chan Zuckerberg Biohub Investigator.

He completed his undergraduate studies in biology at Stanford University, where he worked with Irving Weissman on understanding how the innate immune system recognizes cancer cells. He then entered the Harvard-MIT MD-PhD program, earning his MD from the Harvard-MIT program in Health Sciences and Technology (HST) and his PhD in biology from MIT. His doctoral dissertation with Feng Zhang focused on the discovery and development of CRISPR-Cas enzymes as novel DNA and RNA editing tools. During his final year of medical school, he worked as a visiting scientist with David Baker, where he initiated efforts to design sequence-specific DNA binding proteins de novo.

Following medical school, Cox completed internal medicine residency and a clinical fellowship in hematology at Stanford, where he concurrently conducted postdoctoral research in Rhiju Das's lab. In the Das lab, he fine-tuned large language models for RNA structure prediction and developed new methods for highly multiplexed detection of RNA-protein interactions.

His current list of publications and patents is available here: https://scholar.google.com/citations?user=ZohHoFYAAAAJ&hl=en&oi=ao

Professional Education

  • Fellowship, Stanford University School of Medicine, Hematology (2025)
  • Residency, Stanford University School of Medicine, Internal Medicine (2022)
  • B.Sc., Stanford University, Biology (2009)
  • Ph.D., Massachusetts Institute of Technology, Biology (2018)
  • M.D., Harvard Medical School, Harvard-MIT Health Sciences and Technology (2020)

All Publications

  • Ribonanza: deep learning of RNA structure through dual crowdsourcing. bioRxiv : the preprint server for biology He, S., Huang, R., Townley, J., Kretsch, R. C., Karagianes, T. G., Cox, D. B., Blair, H., Penzar, D., Vyaltsev, V., Aristova, E., Zinkevich, A., Bakulin, A., Sohn, H., Krstevski, D., Fukui, T., Tatematsu, F., Uchida, Y., Jang, D., Lee, J. S., Shieh, R., Ma, T., Martynov, E., Shugaev, M. V., Bukhari, H. S., Fujikawa, K., Onodera, K., Henkel, C., Ron, S., Romano, J., Nicol, J. J., Nye, G. P., Wu, Y., Choe, C., Reade, W., Participants, E., Das, R. 2024

    Abstract

    Prediction of RNA structure from sequence remains an unsolved problem, and progress has been slowed by a paucity of experimental data. Here, we present Ribonanza, a dataset of chemical mapping measurements on two million diverse RNA sequences collected through Eterna and other crowdsourced initiatives. Ribonanza measurements enabled solicitation, training, and prospective evaluation of diverse deep neural networks through a Kaggle challenge, followed by distillation into a single, self-contained model called RibonanzaNet. When fine tuned on auxiliary datasets, RibonanzaNet achieves state-of-the-art performance in modeling experimental sequence dropout, RNA hydrolytic degradation, and RNA secondary structure, with implications for modeling RNA tertiary structure.

    View details for DOI 10.1101/2024.02.24.581671

    View details for PubMedID 38464325

  • Computational design of sequence-specific DNA-binding proteins. bioRxiv : the preprint server for biology Glasscock, C. J., Pecoraro, R., McHugh, R., Doyle, L. A., Chen, W., Boivin, O., Lonnquist, B., Na, E., Politanska, Y., Haddox, H. K., Cox, D., Norn, C., Coventry, B., Goreshnik, I., Vafeados, D., Lee, G. R., Gordan, R., Stoddard, B. L., DiMaio, F., Baker, D. 2023

    Abstract

    Sequence-specific DNA-binding proteins (DBPs) play critical roles in biology and biotechnology, and there has been considerable interest in the engineering of DBPs with new or altered specificities for genome editing and other applications. While there has been some success in reprogramming naturally occurring DBPs using selection methods, the computational design of new DBPs that recognize arbitrary target sites remains an outstanding challenge. We describe a computational method for the design of small DBPs that recognize specific target sequences through interactions with bases in the major groove, and employ this method in conjunction with experimental screening to generate binders for 5 distinct DNA targets. These binders exhibit specificity closely matching the computational models for the target DNA sequences at as many as 6 base positions and affinities as low as 30-100 nM. The crystal structure of a designed DBP-target site complex is in close agreement with the design model, highlighting the accuracy of the design method. The designed DBPs function in both Escherichia coli and mammalian cells to repress and activate transcription of neighboring genes. Our method is a substantial step towards a general route to small and hence readily deliverable sequence-specific DBPs for gene regulation and editing.

    View details for DOI 10.1101/2023.09.20.558720

    View details for PubMedID 37790440

    View details for PubMedCentralID PMC10542524

  • A cytosine deaminase for programmable single-base RNA editing SCIENCE Abudayyeh, O. O., Gootenberg, J. S., Franklin, B., Koob, J., Kellner, M. J., Ladha, A., Joung, J., Kirchgatterer, P., Cox, D. T., Zhang, F. 2019; 365 (6451): 382-+

    Abstract

    Programmable RNA editing enables reversible recoding of RNA information for research and disease treatment. Previously, we developed a programmable adenosine-to-inosine (A-to-I) RNA editing approach by fusing catalytically inactivate RNA-targeting CRISPR-Cas13 (dCas13) with the adenine deaminase domain of ADAR2. Here, we report a cytidine-to-uridine (C-to-U) RNA editor, referred to as RNA Editing for Specific C-to-U Exchange (RESCUE), by directly evolving ADAR2 into a cytidine deaminase. RESCUE doubles the number of mutations targetable by RNA editing and enables modulation of phosphosignaling-relevant residues. We apply RESCUE to drive β-catenin activation and cellular growth. Furthermore, RESCUE retains A-to-I editing activity, enabling multiplexed C-to-U and A-to-I editing through the use of tailored guide RNAs.

    View details for DOI 10.1126/science.aax7063

    View details for Web of Science ID 000477703100041

    View details for PubMedID 31296651

    View details for PubMedCentralID PMC6956565

  • RNA editing with CRISPR-Cas13 SCIENCE Cox, D. T., Gootenberg, J. S., Abudayyeh, O. O., Franklin, B., Kellner, M. J., Joung, J., Zhang, F. 2017; 358 (6366): 1019-1027

    Abstract

    Nucleic acid editing holds promise for treating genetic disease, particularly at the RNA level, where disease-relevant sequences can be rescued to yield functional protein products. Type VI CRISPR-Cas systems contain the programmable single-effector RNA-guided ribonuclease Cas13. We profiled type VI systems in order to engineer a Cas13 ortholog capable of robust knockdown and demonstrated RNA editing by using catalytically inactive Cas13 (dCas13) to direct adenosine-to-inosine deaminase activity by ADAR2 (adenosine deaminase acting on RNA type 2) to transcripts in mammalian cells. This system, referred to as RNA Editing for Programmable A to I Replacement (REPAIR), which has no strict sequence constraints, can be used to edit full-length transcripts containing pathogenic mutations. We further engineered this system to create a high-specificity variant and minimized the system to facilitate viral delivery. REPAIR presents a promising RNA-editing platform with broad applicability for research, therapeutics, and biotechnology.

    View details for DOI 10.1126/science.aaq0180

    View details for Web of Science ID 000416590400033

    View details for PubMedID 29070703

    View details for PubMedCentralID PMC5793859

  • Engineered Cpf1 variants with altered PAM specificities NATURE BIOTECHNOLOGY Gao, L., Cox, D. T., Yan, W. X., Manteiga, J. C., Schneider, M. W., Yamano, T., Nishimasu, H., Nureki, O., Crosetto, N., Zhang, F. 2017; 35 (8): 789-792

    Abstract

    The RNA-guided endonuclease Cpf1 is a promising tool for genome editing in eukaryotic cells. However, the utility of the commonly used Acidaminococcus sp. BV3L6 Cpf1 (AsCpf1) and Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1) is limited by their requirement of a TTTV protospacer adjacent motif (PAM) in the DNA substrate. To address this limitation, we performed a structure-guided mutagenesis screen to increase the targeting range of Cpf1. We engineered two AsCpf1 variants carrying the mutations S542R/K607R and S542R/K548V/N552R, which recognize TYCV and TATV PAMs, respectively, with enhanced activities in vitro and in human cells. Genome-wide assessment of off-target activity using BLISS indicated that these variants retain high DNA-targeting specificity, which we further improved by introducing an additional non-PAM-interacting mutation. Introducing the identified PAM-interacting mutations at their corresponding positions in LbCpf1 similarly altered its PAM specificity. Together, these variants increase the targeting range of Cpf1 by approximately threefold in human coding sequences to one cleavage site per ∼11 bp.

    View details for DOI 10.1038/nbt.3900

    View details for Web of Science ID 000407125800025

    View details for PubMedID 28581492

    View details for PubMedCentralID PMC5548640

  • Diversity and evolution of class 2 CRISPR-Cas systems NATURE REVIEWS MICROBIOLOGY Shmakov, S., Smargon, A., Scott, D., Cox, D., Pyzocha, N., Yan, W., Abudayyeh, O. O., Gootenberg, J. S., Makarova, K. S., Wolf, Y. I., Severinov, K., Zhang, F., Koonin, E. V. 2017; 15 (3): 169-182

    Abstract

    Class 2 CRISPR-Cas systems are characterized by effector modules that consist of a single multidomain protein, such as Cas9 or Cpf1. We designed a computational pipeline for the discovery of novel class 2 variants and used it to identify six new CRISPR-Cas subtypes. The diverse properties of these new systems provide potential for the development of versatile tools for genome editing and regulation. In this Analysis article, we present a comprehensive census of class 2 types and class 2 subtypes in complete and draft bacterial and archaeal genomes, outline evolutionary scenarios for the independent origin of different class 2 CRISPR-Cas systems from mobile genetic elements, and propose an amended classification and nomenclature of CRISPR-Cas.

    View details for DOI 10.1038/nrmicro.2016.184

    View details for Web of Science ID 000394281600011

    View details for PubMedID 28111461

    View details for PubMedCentralID PMC5851899

  • Cas13b Is a Type VI-B CRISPR-Associated RNA-Guided RNase Differentially Regulated by Accessory Proteins Csx27 and Csx28 MOLECULAR CELL Smargon, A. A., Cox, D. T., Pyzocha, N. K., Zheng, K., Slaymaker, I. M., Gootenberg, J. S., Abudayyeh, O. A., Essletzbichler, P., Shmakov, S., Makarova, K. S., Koonin, E. V., Zhang, F. 2017; 65 (4): 618-+

    Abstract

    CRISPR-Cas adaptive immune systems defend microbes against foreign nucleic acids via RNA-guided endonucleases. Using a computational sequence database mining approach, we identify two class 2 CRISPR-Cas systems (subtype VI-B) that lack Cas1 and Cas2 and encompass a single large effector protein, Cas13b, along with one of two previously uncharacterized associated proteins, Csx27 and Csx28. We establish that these CRISPR-Cas systems can achieve RNA interference when heterologously expressed. Through a combination of biochemical and genetic experiments, we show that Cas13b processes its own CRISPR array with short and long direct repeats, cleaves target RNA, and exhibits collateral RNase activity. Using an E. coli essential gene screen, we demonstrate that Cas13b has a double-sided protospacer-flanking sequence and elucidate RNA secondary structure requirements for targeting. We also find that Csx27 represses, whereas Csx28 enhances, Cas13b-mediated RNA interference. Characterization of these CRISPR systems creates opportunities to develop tools to manipulate and monitor cellular transcripts.

    View details for DOI 10.1016/j.molcel.2016.12.023

    View details for Web of Science ID 000396431500006

    View details for PubMedID 28065598

    View details for PubMedCentralID PMC5432119

  • RNA targeting with CRISPR-Cas13. Nature Abudayyeh, O. O., Gootenberg, J. S., Essletzbichler, P. n., Han, S. n., Joung, J. n., Belanto, J. J., Verdine, V. n., Cox, D. B., Kellner, M. J., Regev, A. n., Lander, E. S., Voytas, D. F., Ting, A. Y., Zhang, F. n. 2017; 550 (7675): 280–84

    Abstract

    RNA has important and diverse roles in biology, but molecular tools to manipulate and measure it are limited. For example, RNA interference can efficiently knockdown RNAs, but it is prone to off-target effects, and visualizing RNAs typically relies on the introduction of exogenous tags. Here we demonstrate that the class 2 type VI RNA-guided RNA-targeting CRISPR-Cas effector Cas13a (previously known as C2c2) can be engineered for mammalian cell RNA knockdown and binding. After initial screening of 15 orthologues, we identified Cas13a from Leptotrichia wadei (LwaCas13a) as the most effective in an interference assay in Escherichia coli. LwaCas13a can be heterologously expressed in mammalian and plant cells for targeted knockdown of either reporter or endogenous transcripts with comparable levels of knockdown as RNA interference and improved specificity. Catalytically inactive LwaCas13a maintains targeted RNA binding activity, which we leveraged for programmable tracking of transcripts in live cells. Our results establish CRISPR-Cas13a as a flexible platform for studying RNA in mammalian cells and therapeutic development.

    View details for PubMedID 28976959

    View details for PubMedCentralID PMC5706658

  • Engineering and optimising deaminase fusions for genome editing NATURE COMMUNICATIONS Yang, L., Briggs, A. W., Chew, W., Mali, P., Guell, M., Aach, J., Goodman, D., Cox, D., Kan, Y., Lesha, E., Soundararajan, V., Zhang, F., Church, G. 2016; 7: 13330

    Abstract

    Precise editing is essential for biomedical research and gene therapy. Yet, homology-directed genome modification is limited by the requirements for genomic lesions, homology donors and the endogenous DNA repair machinery. Here we engineered programmable cytidine deaminases and test if we could introduce site-specific cytidine to thymidine transitions in the absence of targeted genomic lesions. Our programmable deaminases effectively convert specific cytidines to thymidines with 13% efficiency in Escherichia coli and 2.5% in human cells. However, off-target deaminations were detected more than 150 bp away from the target site. Moreover, whole genome sequencing revealed that edited bacterial cells did not harbour chromosomal abnormalities but demonstrated elevated global cytidine deamination at deaminase intrinsic binding sites. Therefore programmable deaminases represent a promising genome editing tool in prokaryotes and eukaryotes. Future engineering is required to overcome the processivity and the intrinsic DNA binding affinity of deaminases for safer therapeutic applications.

    View details for DOI 10.1038/ncomms13330

    View details for Web of Science ID 000386651600001

    View details for PubMedID 27804970

    View details for PubMedCentralID PMC5097136

  • C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector SCIENCE Abudayyeh, O. O., Gootenberg, J. S., Konermann, S., Joung, J., Slaymaker, I. M., Cox, D. T., Shmakov, S., Makarova, K. S., Semenova, E., Minakhin, L., Severinov, K., Regev, A., Lander, E. S., Koonin, E. V., Zhang, F. 2016; 353 (6299): aaf5573

    Abstract

    The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated genes (Cas) adaptive immune system defends microbes against foreign genetic elements via DNA or RNA-DNA interference. We characterize the class 2 type VI CRISPR-Cas effector C2c2 and demonstrate its RNA-guided ribonuclease function. C2c2 from the bacterium Leptotrichia shahii provides interference against RNA phage. In vitro biochemical analysis shows that C2c2 is guided by a single CRISPR RNA and can be programmed to cleave single-stranded RNA targets carrying complementary protospacers. In bacteria, C2c2 can be programmed to knock down specific mRNAs. Cleavage is mediated by catalytic residues in the two conserved Higher Eukaryotes and Prokaryotes Nucleotide-binding (HEPN) domains, mutations of which generate catalytically inactive RNA-binding proteins. These results broaden our understanding of CRISPR-Cas systems and suggest that C2c2 can be used to develop new RNA-targeting tools.

    View details for DOI 10.1126/science.aaf5573

    View details for Web of Science ID 000381560900032

    View details for PubMedID 27256883

    View details for PubMedCentralID PMC5127784

  • The Progranulin Cleavage Products, Granulins, Exacerbate TDP-43 Toxicity and Increase TDP-43 Levels. The Journal of neuroscience : the official journal of the Society for Neuroscience Salazar, D. A., Butler, V. J., Argouarch, A. R., Hsu, T. Y., Mason, A., Nakamura, A., McCurdy, H., Cox, D., Ng, R., Pan, G., Seeley, W. W., Miller, B. L., Kao, A. W. 2015; 35 (25): 9315-28

    Abstract

    Mutations in the human progranulin gene resulting in protein haploinsufficiency cause frontotemporal lobar degeneration with TDP-43 inclusions. Although progress has been made in understanding the normal functions of progranulin and TDP-43, the molecular interactions between these proteins remain unclear. Progranulin is proteolytically processed into granulins, but the role of granulins in the pathogenesis of neurodegenerative disease is unknown. We used a Caenorhabditis elegans model of neuronal TDP-43 proteinopathy to specifically interrogate the contribution of granulins to the neurodegenerative process. Complete loss of the progranulin gene did not worsen TDP-43 toxicity, whereas progranulin heterozygosity did. Interestingly, expression of individual granulins alone had little effect on behavior. In contrast, when granulins were coexpressed with TDP-43, they exacerbated its toxicity in a variety of behaviors including motor coordination. These same granulins increased TDP-43 levels via a post-translational mechanism. We further found that in human neurodegenerative disease subjects, granulin fragments accumulated specifically in diseased regions of brain. To our knowledge, this is the first demonstration of a toxic role for granulin fragments in a neurodegenerative disease model. These studies suggest that presence of cleaved granulins, rather than or in addition to loss of full-length progranulin, may contribute to disease in TDP-43 proteinopathies.

    View details for DOI 10.1523/JNEUROSCI.4808-14.2015

    View details for PubMedID 26109656

    View details for PubMedCentralID PMC4478251

  • CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus SCIENTIFIC REPORTS Ramanan, V., Shlomai, A., Cox, D. T., Schwartz, R. E., Michailidis, E., Bhatta, A., Scott, D. A., Zhang, F., Rice, C. M., Bhatia, S. N. 2015; 5: 10833

    Abstract

    Chronic hepatitis B virus (HBV) infection is prevalent, deadly, and seldom cured due to the persistence of viral episomal DNA (cccDNA) in infected cells. Newly developed genome engineering tools may offer the ability to directly cleave viral DNA, thereby promoting viral clearance. Here, we show that the CRISPR/Cas9 system can specifically target and cleave conserved regions in the HBV genome, resulting in robust suppression of viral gene expression and replication. Upon sustained expression of Cas9 and appropriately chosen guide RNAs, we demonstrate cleavage of cccDNA by Cas9 and a dramatic reduction in both cccDNA and other parameters of viral gene expression and replication. Thus, we show that directly targeting viral episomal DNA is a novel therapeutic approach to control the virus and possibly cure patients.

    View details for DOI 10.1038/srep10833

    View details for Web of Science ID 000355614400001

    View details for PubMedID 26035283

    View details for PubMedCentralID PMC4649911

  • Therapeutic genome editing: prospects and challenges NATURE MEDICINE Cox, D., Platt, R., Zhang, F. 2015; 21 (2): 121-131

    Abstract

    Recent advances in the development of genome editing technologies based on programmable nucleases have substantially improved our ability to make precise changes in the genomes of eukaryotic cells. Genome editing is already broadening our ability to elucidate the contribution of genetics to disease by facilitating the creation of more accurate cellular and animal models of pathological processes. A particularly tantalizing application of programmable nucleases is the potential to directly correct genetic mutations in affected tissues and cells to treat diseases that are refractory to traditional therapies. Here we discuss current progress toward developing programmable nuclease-based therapies as well as future prospects and challenges.

    View details for DOI 10.1038/nm.3793

    View details for Web of Science ID 000348974800014

    View details for PubMedID 25654603

    View details for PubMedCentralID PMC4492683

  • RNA-guided editing of bacterial genomes using CRISPR-Cas systems NATURE BIOTECHNOLOGY Jiang, W., Bikard, D., Cox, D., Zhang, F., Marraffini, L. A. 2013; 31 (3): 233-239

    Abstract

    Here we use the clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated Cas9 endonuclease complexed with dual-RNAs to introduce precise mutations in the genomes of Streptococcus pneumoniae and Escherichia coli. The approach relies on dual-RNA:Cas9-directed cleavage at the targeted genomic site to kill unmutated cells and circumvents the need for selectable markers or counter-selection systems. We reprogram dual-RNA:Cas9 specificity by changing the sequence of short CRISPR RNA (crRNA) to make single- and multinucleotide changes carried on editing templates. Simultaneous use of two crRNAs enables multiplex mutagenesis. In S. pneumoniae, nearly 100% of cells that were recovered using our approach contained the desired mutation, and in E. coli, 65% that were recovered contained the mutation, when the approach was used in combination with recombineering. We exhaustively analyze dual-RNA:Cas9 target requirements to define the range of targetable sequences and show strategies for editing sites that do not meet these requirements, suggesting the versatility of this technique for bacterial genome engineering.

    View details for DOI 10.1038/nbt.2508

    View details for Web of Science ID 000316439500018

    View details for PubMedID 23360965

  • Multiplex Genome Engineering Using CRISPR/Cas Systems SCIENCE Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., Zhang, F. 2013; 339 (6121): 819-823

    Abstract

    Functional elucidation of causal genetic variants and elements requires precise genome editing technologies. The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage. We engineered two different type II CRISPR/Cas systems and demonstrate that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells. Cas9 can also be converted into a nicking enzyme to facilitate homology-directed repair with minimal mutagenic activity. Lastly, multiple guide sequences can be encoded into a single CRISPR array to enable simultaneous editing of several sites within the mammalian genome, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology.

    View details for DOI 10.1126/science.1231143

    View details for Web of Science ID 000314874400049

    View details for PubMedID 23287718