About

Jennifer A. Doudna is a Professor of Chemistry at the University of California, Berkeley, holding the Li Ka Shing Chancellor’s Chair in Biomedical and Health Sciences. She is a Nobel Laureate in Chemistry, recognized for her pioneering work in the discovery of CRISPR, a revolutionary gene-editing technology. Her research focuses on advancing society through education and research in the fields of chemical biology, molecular and cell biology, and biomedical sciences. Doudna's academic career includes post-doctoral work at the University of Colorado, followed by positions at Yale University, where she served as an assistant, associate, and full professor before joining UC Berkeley in 2002. She has been a Howard Hughes Medical Investigator since 1997 and has received numerous awards, including the NSF Alan T. Waterman Award in 2000, and membership in prestigious organizations such as the National Academy of Sciences, the American Academy of Arts and Sciences, and the Institute of Medicine of the National Academies. Her groundbreaking research has significantly contributed to the development and understanding of CRISPR technology, impacting the fields of genetics, molecular biology, and biomedical sciences.

Research topics

• Biology
• Computational biology
• Genetics
• Cell biology
• Chemistry

Selected publications

• Identification of proteins influencing CRISPR-associated transposases for enhanced genome editing

  Science Advances · 2026-01-01 · 2 citations

  articleOpen access

  CRISPR-associated transposases (CASTs) hold tremendous potential for microbial genome editing because of their ability to integrate large DNA cargos in a programmable, site-specific manner. However, their widespread application has been hindered by poorly understood host factor requirements for transposition. To address this gap, we conducted the first genome-wide screen for host factors affecting Vibrio cholerae CAST ( Vch CAST) activity using an Escherichia coli RB-TnSeq library and identified 15 genes affecting Vch CAST transposition. Of these, seven factors were validated to improve Vch CAST activity, and two were inhibitory. Guided by the identification of homologous recombination effectors, RecD and RecA, we tested the λ-Red recombineering system in our Vch CAST editing vectors and increased editing efficiency by 55.2-fold in E. coli , 5.6-fold in Pseudomonas putida , and 10.8-fold in Klebsiella michiganensis while maintaining high target specificity and similar insertion arrangements. This study improves the understanding of factors affecting Vch CAST activity and enhances its efficiency as a bacterial genome editor.

  PublisherDOI

• Efficient transgene-free multiplexed germline editing via viral delivery of an engineered TnpB

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-23 · 1 citations

  articleOpen access

  Abstract Virus-induced genome editing (VIGE) using compact RNA-guided endonucleases is a transformational new approach in plant biotechnology, enabling tissue-culture-independent and transgene-free genome editing (Hu et al. 2025; Liu et al. 2025; Weiss et al. 2025). We recently established a VIGE approach for heritable editing at single loci in Arabidopsis by delivering the compact genome editor ISYmu1 TnpB (Ymu1) and its guide RNA (gRNA) via Tobacco Rattle Virus (TRV) (Weiss et al. 2025). Here, we greatly improved this approach by devising a multiple gRNA expression system and by utilizing an engineered high-activity Ymu1 variant (Ymu1-WFR) (Zhou et al. 2026) to develop an efficient multiplexed genome editing platform.

  PublisherDOI

• Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-14 · 4 citations

  preprintOpen access

  Primary human myeloid cells are promising candidates for immunotherapy, yet efficient and scalable technologies for genetic engineering and screening in these cells are limited. Here we present a virus-like particle (VLP)-based toolkit that delivers diverse CRISPR genome editing modalities to human monocytes, macrophages, and dendritic cells with high efficiency while preserving viability and innate immune responsiveness. VLP-mediated delivery of ribonucleoprotein payloads supports gene knockout, base editing and epigenetic silencing, and enables site-specific integration of large DNA sequences when combined with AAV donors for homology-directed repair. Leveraging sgRNA delivery via VPX-lentivirus combined with Cas9 protein delivery via engineered virus-like particle (eVLP) treatment ("SLICeVLP"), we performed the first pooled loss-of-function screens in human macrophages. We uncovered regulators of TNF production and CD80 expression in human macrophages, converging on TNFAIP3 as a central regulator of inflammatory polarization. TNFAIP3 ablation promoted a pro-inflammatory cell state that is resistant to suppressive polarization, and augmented cytotoxicity of engineered HER2 CAR-macrophages. Taken together, this technology platform enables unbiased discovery and characterization of functional gene targets in primary human myeloid cells.

  PublisherOA PDFDOI

• Phage-based delivery of CRISPR-associated transposases for targeted bacterial editing

  Proceedings of the National Academy of Sciences · 2025-07-25 · 19 citations

  articleOpen access

  Phage λ, a well-characterized temperate phage, has been recently leveraged for bacterial genome editing by selectively delivering base editors into targeted bacterial species. We extend this concept by engineering phage λ to deliver CRISPR-guided transposases, accomplishing large insertions and targeted gene disruptions. To achieve this, we engineered phage λ using homologous recombination paired with Cas13a-based counterselection for precise phage modifications. Initially, we established the utility of Cas13a in phage λ by conducting minimal recoding edits, deletions, and insertions. Subsequently, we scaled up the engineering to embed the comprehensive DNA-editing CRISPR-Cas transposase (DART) system within the phage genome, creating λ-DART phages. These modified λ-DART phages were then employed to infect Escherichia coli , generating CRISPR RNA-guided transposition events in the host genome. Applying our engineered λ-DART phages to monocultures and a mixed bacterial community comprising three genera led to efficient, precise, and specific gene knockouts and insertions in the targeted E. coli cells, achieving editing efficiencies surpassing 50% of the population. This research enhances phage-mediated genome editing by enabling efficient in situ gene integrations in bacteria, offering an avenue for further application in microbial community contexts. This scalable method enables flexible microbial genome editing in situ to manipulate the function and composition of diverse ecosystems.

  PublisherDOI

• Viral delivery of an RNA-guided genome editor for transgene-free germline editing in Arabidopsis

  Nature Plants · 2025-04-22 · 70 citations

  articleOpen access

  Abstract Genome editing is transforming plant biology by enabling precise DNA modifications. However, delivery of editing systems into plants remains challenging, often requiring slow, genotype-specific methods such as tissue culture or transformation 1 . Plant viruses, which naturally infect and spread to most tissues, present a promising delivery system for editing reagents. However, many viruses have limited cargo capacities, restricting their ability to carry large CRISPR-Cas systems. Here we engineered tobacco rattle virus (TRV) to carry the compact RNA-guided TnpB enzyme ISYmu1 and its guide RNA. This innovation allowed transgene-free editing of Arabidopsis thaliana in a single step, with edits inherited in the subsequent generation. By overcoming traditional reagent delivery barriers, this approach offers a novel platform for genome editing, which can greatly accelerate plant biotechnology and basic research.

  PublisherOA PDFDOI

• Divergent viral phosphodiesterases for immune signaling evasion

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-21

  preprintOpen accessSenior authorCorresponding

  Cyclic dinucleotides (CDNs) and other short oligonucleotides play fundamental roles in immune system activation in organisms ranging from bacteria to humans. In response, viruses use phosphodiesterase-mediated oligonucleotide cleavage for immune evasion, a strategy whose diversity has not yet been explored. We used a canonical 2H phosphodiesterase (2H PDE) structure-based search of prokaryotic and eukaryotic viral sequences to identify an exceptional diversity of 2H PDEs across the virome, including enzymes not detectable with sequence search methods alone. Despite active site conservation, biochemical experiments revealed remarkable substrate specificity of these PDEs that corresponds to variation in the core 2H fold. This nuanced specificity allows 2H PDEs to selectively degrade oligonucleotide messengers to avoid interfering with host immune signaling. Together, these findings nominate viral 2H PDEs as key regulators of CDN signaling across the tree of life.

  PublisherOA PDFDOI

• Improving RNA Secondary Structure Prediction Through Expanded Training Data

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-03 · 1 citations

  preprintOpen access

  In recent years, deep learning has revolutionized protein structure prediction, achieving remarkable speed and accuracy. RNA structure prediction, however, has lagged behind. Although several methods have shown some success in predicting RNA secondary and tertiary structures, none have reached the accuracy observed with contemporary protein models. The lack of success of these RNA structure prediction models has been proposed to be due to limited high-quality structural information that can be used as training data. To probe this proposed limitation, we developed a large and diverse dataset comprising paired RNA sequences and their corresponding secondary structures. We assess the utility of this enhanced dataset by retraining on a deep learning model, SincFold. We find that SincFold exhibited improved generalization to some previously unseen RNA families, enhancing its capability to predict accurate de novo RNA secondary structures. The RNASSTR dataset provides a substantial advance for RNA structure modeling, laying a strong foundation for the development of future RNA secondary structure prediction algorithms.

  PublisherOA PDFDOI

• An updated evolutionary classification of CRISPR–Cas systems including rare variants

  Nature Microbiology · 2025-11-06 · 44 citations

  reviewOpen access

  The known diversity of CRISPR-Cas systems continues to expand. To encompass new discoveries, here we present an updated evolutionary classification of CRISPR-Cas systems. The updated CRISPR-Cas classification includes 2 classes, 7 types and 46 subtypes, compared with the 6 types and 33 subtypes in our previous survey 5 years ago. In addition, a classification of the cyclic oligoadenylate-dependent signalling pathway in type III systems is presented. We also discuss recently characterized alternative CRISPR-Cas functionalities, notably, type IV variants that cleave the target DNA and type V variants that inhibit the target replication without cleavage. Analysis of the abundance of CRISPR-Cas variants in genomes and metagenomes shows that the previously defined systems are relatively common, whereas the more recently characterized variants are comparatively rare. These low abundance variants comprise the long tail of the CRISPR-Cas distribution in prokaryotes and their viruses, and remain to be characterized experimentally.

  PublisherOA PDFDOI

• Directed evolution expands CRISPR–Cas12a genome-editing capacity

  Nucleic Acids Research · 2025-07-08 · 13 citations

  articleOpen accessSenior author

  CRISPR-Cas12a enzymes are versatile RNA-guided genome-editing tools with applications encompassing viral diagnosis, agriculture, and human therapeutics. However, their dependence on a 5'-TTTV-3' protospacer adjacent motif (PAM) next to DNA target sequences restricts Cas12a's gene targeting capability to only ∼1% of a typical genome. To mitigate this constraint, we used a bacterial-based directed evolution assay combined with rational engineering to identify variants of Lachnospiraceae bacterium Cas12a with expanded PAM recognition. The resulting Cas12a variants use a range of noncanonical PAMs while retaining recognition of the canonical 5'-TTTV-3' PAM. In particular, biochemical and cell-based assays show that the variant Flex-Cas12a utilizes 5'-NYHV-3' PAMs that expand DNA recognition sites to ∼25% of the human genome. With enhanced targeting versatility, Flex-Cas12a unlocks access to previously inaccessible genomic loci, providing new opportunities for both therapeutic and agricultural genome engineering.

  PublisherDOI

• Atlas of CRISPR Correction of Pathogenic Human Genetic Variants

  Research Square · 2025-03-24

  preprintOpen access
  PublisherOA PDFDOI

Frequent coauthors

• Jillian F. Banfield

  University of California, Berkeley

  331 shared

• Abdullah M. Syed

  Gladstone Institutes

  311 shared

• Alison Ciling

  University of California, Berkeley

  294 shared

• Eva Nogales

  Howard Hughes Medical Institute

  294 shared

• Mélanie Ott

  Gladstone Institutes

  284 shared

• Benjamin A. Adler

  Innovative Genomics Institute

  277 shared

• Gavin J. Knott

  Monash University

  260 shared

• Marena Trinidad

  Howard Hughes Medical Institute

  254 shared

Awards & honors

• Howard Hughes Medical Investigator (1997 to present)
• Packard Foundation Fellow Award (1996)
• NSF Alan T. Waterman Award (2000)
• Member, National Academy of Sciences (2002)
• Member, American Academy of Arts and Sciences (2003)