J. A. Doudna

Regulation of virion production by the ORF8 signal peptide across SARS-CoV-2 variants

This study shows ORF8 suppresses viral particle production by interacting with Spike and causing Golgi fragmentation, supporting evolutionary pressure to delete ORF8 in SARS-CoV-2 variants.

Hachiman is a genome integrity sensor

This study identifies Hachiman as a bacterial antiphage defense system that degrades all DNA in response to DNA damage, revealing its role as a genome integrity sensor.

Birth of new protein folds and functions in the virome

The paper identifies new viral protein folds and functions by analyzing a database of predicted viral protein structures, revealing conserved immune evasion mechanisms across different viral species.

Assembly reactions of SARS-CoV-2 nucleocapsid protein with nucleic acid

This study investigates the assembly of SARS-CoV-2 nucleocapsid protein with nucleic acids using biophysical techniques and mutant proteins, revealing key interaction motifs and stabilization mechanisms.

Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR-Cas9 RNP

This study demonstrates that lipid nanoparticle-delivered thermostable Cas9 RNPs achieve high-efficiency genome editing in mouse liver and lung tissues.

Engineering self-deliverable ribonucleoproteins for genome editing in the brain

This study engineers self-deliverable CRISPR ribonucleoproteins for efficient genome editing in neural progenitor cells and mouse brain tissue.

A phage nucleus-associated RNA-binding protein is required for jumbo phage infection

This study identifies ChmC, a phage protein that binds RNA and facilitates mRNA transport through the phage nucleus-like compartment, essential for infection.

Genome-wide Characterization of Diverse Bacteriophages Enabled by RNA-Binding CRISPRi

The paper develops a CRISPRi-ART system to knock down protein expression in diverse bacteriophages and identifies essential genes, including many with unknown functions.

Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs

This study demonstrates that minimally immunogenic Cas9 RNPs delivered via convection enhanced delivery can edit mouse striatal neurons with reduced immune responses compared to AAV-delivered Cas9.

Mitigation of chromosome loss in clinical CRISPR-Cas9-engineered T cells

This study investigates chromosome loss in CRISPR-Cas9-engineered T cells and shows a modified manufacturing process reduces it while preserving editing efficacy.

Genomic analysis of cultivated infant microbiomes identifies Bifidobacterium 2'-fucosyllactose utilization can be facilitated by co-existing species

The paper shows that Bifidobacterium breve can utilize 2'-fucosyllactose with help from co-existing species like Ruminococcus gnavus in infant microbiomes.

Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6

The paper introduces a plasmid-based method to assemble SARS-CoV-2 genomes and identifies NSP6 mutations as causing Omicron attenuation.

Genome expansion by a CRISPR trimmer-integrase

The paper identifies a CRISPR trimmer-integrase that processes DNA for integration in the absence of Cas4, using cryo-EM structures to show its mechanism.

Genome editing in plants using the compact editor Cas{Phi}

This paper demonstrates that the hypercompact Cas{Phi} nuclease can generate heritable gene edits in Arabidopsis with high specificity and efficiency, and shows that its performance is influenced by chromatin environment and temperature.

Improved Genome Editing by an Engineered CRISPR-Cas12a

This paper improves CRISPR-Cas12a genome editing by combining rational engineering and directed evolution to enhance homology-directed repair efficiency.

Precise Transcript Targeting by CRISPR-Csm Complexes

This study demonstrates that the CRISPR-Csm complex efficiently and precisely targets and degrades both nuclear and cytoplasmic transcripts in human cells with minimal off-target effects.

RNA-targeting CRISPR-Cas13 Provides Broad-spectrum Phage Immunity

This paper demonstrates that LbuCas13a can broadly inhibit diverse E. coli phages and enable efficient, markerless phage genome editing.

Crystal structure of an RNA/DNA strand exchange junction

The paper reports the X-ray crystal structure of an RNA/DNA strand exchange junction, revealing structural principles of A-to-B helical transitions in RNA/DNA hybrids.

A naturally DNase-free CRISPR-Cas12c enzyme silences gene expression

This paper shows that CRISPR-Cas12c provides antiviral immunity by binding DNA without cleaving it, enabling transcriptional repression and phage protection.

CRISPR-Cas9 mediated nuclear transport and genomic integration of nanostructured genes in human primary cells

This study delivers DNA nanostructures into human primary cells using CRISPR-Cas9, achieving efficient genomic integration with lower toxicity than dsDNA.

CRISPR-Cas9 bends and twists DNA to read its sequence

This paper reveals how CRISPR-Cas9 bends and twists DNA to flip nucleotides toward guide RNA for sequence interrogation.

Rapid assessment of SARS-CoV-2 evolved variants using virus-like particles

This study uses SARS-CoV-2 virus-like particles to rapidly assess mutations in viral variants, finding that N protein mutations enhance RNA packaging and viral spread.

Borgs are giant extrachromosomal elements with the potential to augment methane oxidation

The paper identifies Borgs, large extrachromosomal elements in Methanoperedens archaea, which enhance methane oxidation capacity and may influence greenhouse gas emissions.

Diverse ATPase proteins in mobilomes constitute a large potential sink for prokaryotic host ATP

The paper identifies ATPase proteins in mobilome genomes as potential energy sinks that may suppress host energy consumption during replication.

Cancer-specific loss of TERT activation sensitizes glioblastoma to DNA damage

This study shows that reducing GABPB1L in TERT-mutant glioblastomas, combined with chemotherapy, reduces tumor growth by impairing DNA damage response.

Structural coordination between active sites of a Cas6-reverse transcriptase-Cas1--Cas2 CRISPR integrase complex

The paper determines the cryo-EM structure of a Cas6-RT-Cas1-Cas2 complex and shows bidirectional and unidirectional crosstalk between its active sites.

Quantification of Cas9 binding and cleavage across diverse guide sequences maps landscapes of target engagement

The paper quantifies Cas9 binding and cleavage across diverse guide sequences, revealing sequence-specific variations in efficacy and specificity, and develops a predictive biophysical model.

Targeted Genome Editing of Bacteria Within Microbial Communities

This paper develops a method to edit specific bacteria within microbial communities using ET-Seq and DART systems, enabling genetic manipulation in complex environments.

Huge and variable diversity of episymbiotic CPR bacteria and DPANN archaea in groundwater ecosystems

The paper characterizes CPR bacteria and DPANN archaea in groundwater ecosystems, finding high diversity and site-specific variation, with potential health implications.

CRISPR-Cas12a exploits R-loop asymmetry to form double strand breaks

This study shows that Cas12a uses R-loop asymmetry to cut the second DNA strand without direct protein interaction, explaining its double-strand break mechanism.