Correspondence |
Featured
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Correspondence |
What does it take for an ‘AlphaFold Moment’ in functional protein engineering and design?
- Roberto A. Chica
- & Noelia Ferruz
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Research Briefing |
A conditional, zinc-finger-dependent recombinase system for DNA editing
By applying the logic of conditional enzymes, we have developed a zinc-finger-dependent recombinase system, the editing activity of which is induced by zinc finger DNA binding. The system combines the precision of recombinases with the DNA target site programmability of zinc finger domains.
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Research Briefing |
Computer-based design of sensors that can monitor endogenous Ras activity
Many questions on the activity of the Ras proto-oncogene are unanswered due to the lack of tools for detecting active Ras in living cells. Here, we used protein design and structure prediction algorithms to develop biosensors that detect the activity and environment of endogenous Ras.
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Article
| Open Access
Computationally designed sensors detect endogenous Ras activity and signaling effectors at subcellular resolution
Computationally designed sensors map the activity and signaling environment of Ras.
- Jason Z. Zhang
- , William H. Nguyen
- & David Baker
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Article |
Engineered serum markers for non-invasive monitoring of gene expression in the brain
Gene expression in the mouse brain is measured with a simple blood draw.
- Sangsin Lee
- , Shirin Nouraein
- & Jerzy O. Szablowski
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Research Briefing |
Generation of programmable splicing factors using RNA-binding proteins that activate exon inclusion
We developed luciferase-based splicing reporters to evaluate 718 RNA-binding proteins (RBPs) for the ability to activate exon inclusion. Our screen detected RBPs with no previously characterized roles in splicing and utilized RBP domains displaying potent exon activation to develop programmable splicing modulators with improved strength, generalizability and size over previous versions.
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Article
| Open Access
Large-scale evaluation of the ability of RNA-binding proteins to activate exon inclusion
Alternative splicing is controlled with engineered fusion splicing factors.
- Jonathan C. Schmok
- , Manya Jain
- & Gene W. Yeo
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Article |
Strand-preferred base editing of organellar and nuclear genomes using CyDENT
A TALE-based modular base editing system shows high strand specificity in multiple organelles.
- Jiacheng Hu
- , Yu Sun
- & Caixia Gao
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Research Briefing |
Efficient A-to-C base editing with high specificity
Generating A-to-C transversions in specific targets via base editing technology has been challenging. By fusing an evolved alkyladenine DNA glycosylase with an engineered adenine deaminase TadA-8e variant and nickase Cas9, we have developed A-to-C base editors that generate precise and efficient A-to-C transversions in cells and in mouse embryos, expanding the possible applications of base editing.
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Article |
Adenine transversion editors enable precise, efficient A•T-to-C•G base editing in mammalian cells and embryos
A base editor for precise adenine transversions is demonstrated in mouse embryos.
- Liang Chen
- , Mengjia Hong
- & Dali Li
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Article
| Open Access
Genetically encoded barcodes for correlative volume electron microscopy
Multiplexable barcodes for electron microscopy are applied to brain imaging.
- Felix Sigmund
- , Oleksandr Berezin
- & Gil Gregor Westmeyer
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Article |
Targeted DNA integration in human cells without double-strand breaks using CRISPR-associated transposases
Large DNA sequences are integrated into human cells using RNA-guided CRISPR-associated transposases.
- George D. Lampe
- , Rebeca T. King
- & Samuel H. Sternberg
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Article
| Open Access
Prediction of prime editing insertion efficiencies using sequence features and DNA repair determinants
Prime editing efficiency is affected by insertion sequence features, secondary structure and DNA repair context.
- Jonas Koeppel
- , Juliane Weller
- & Leopold Parts
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Article
| Open Access
A universal deep-learning model for zinc finger design enables transcription factor reprogramming
Zinc finger design is facilitated with a deep-learning model.
- David M. Ichikawa
- , Osama Abdin
- & Marcus B. Noyes
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Article
| Open Access
Engineered live bacteria suppress Pseudomonas aeruginosa infection in mouse lung and dissolve endotracheal-tube biofilms
A bacterium expressing antibacterial genes treats a lung infection associated with mechanical ventilators.
- Rocco Mazzolini
- , Irene Rodríguez-Arce
- & Maria Lluch-Senar
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Article |
Tension-tuned receptors for synthetic mechanotransduction and intercellular force detection
Synthetic sensors of extra and intracellular mechanical forces that activate gene expression are designed.
- D. Christopher Sloas
- , Jeremy C. Tran
- & John T. Ngo
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Brief Communication |
Programmable A-to-Y base editing by fusing an adenine base editor with an N-methylpurine DNA glycosylase
A base editor is engineered for A-to-T and A-to-C transversion editing.
- Huawei Tong
- , Xuchen Wang
- & Hui Yang
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Article
| Open Access
Improved cytosine base editors generated from TadA variants
Improved cytosine base editors are generated by directed evolution of an adenosine deaminase.
- Dieter K. Lam
- , Patricia R. Feliciano
- & Nicole M. Gaudelli
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News & Views |
Writing cellular history in protein chains
Elongating protein fibers record the transcriptional activity of single cells for later readout by imaging.
- Hyung-Bae Kwon
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Research Briefing |
Real-time monitoring of tumor-homing bacteria and tumor cells in vivo using ultrasound
By screening natural prokaryotic gas vesicle gene clusters, we found and engineered new acoustic reporter genes (ARGs) that give bacteria and mammalian cells brighter ultrasound contrast for real-time noninvasive imaging. Expressing these ARGs in engineered cells enabled us to image tumor-homing bacteria and perform genetically guided tumor biopsies in vivo.
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Article
| Open Access
Recording of cellular physiological histories along optically readable self-assembling protein chains
A history of cellular events is recorded in self-assembling protein chains.
- Changyang Linghu
- , Bobae An
- & Edward S. Boyden
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Article |
Time-tagged ticker tapes for intracellular recordings
Reporter gene expression history in cells is recorded with engineered fluorescent protein fibers.
- Dingchang Lin
- , Xiuyuan Li
- & Adam E. Cohen
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Article |
Drag-and-drop genome insertion of large sequences without double-strand DNA cleavage using CRISPR-directed integrases
Large sequences are integrated site specifically into the human genome without double-strand DNA cleavage.
- Matthew T. N. Yarnall
- , Eleonora I. Ioannidi
- & Jonathan S. Gootenberg
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Brief Communication |
High-throughput retrieval of target sequences from complex clone libraries using CRISPRi
A CRISPRi method retrieves sequences of interest from large metagenomic libraries.
- Ján Burian
- , Vincent K. Libis
- & Sean F. Brady
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Article
| Open Access
An engineered T7 RNA polymerase that produces mRNA free of immunostimulatory byproducts
The purity of synthetic mRNA is improved with a double-mutant T7 RNA polymerase.
- Athanasios Dousis
- , Kanchana Ravichandran
- & Amy E. Rabideau
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Article
| Open Access
Precision mitochondrial DNA editing with high-fidelity DddA-derived base editors
Off-target activity of DddA-derived base editors is minimized through protein engineering.
- Seonghyun Lee
- , Hyunji Lee
- & Jin-Soo Kim
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Article |
Modular, programmable RNA sensing using ADAR editing in living cells
Specific RNAs are detected in live cells by harnessing endogenous ADAR enzymes.
- K. Eerik Kaseniit
- , Noa Katz
- & Xiaojing J. Gao
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Brief Communication |
Engineered CRISPR prime editors with compact, untethered reverse transcriptases
A split prime editor architecture facilitates screening and engineering of improved variants.
- Julian Grünewald
- , Bret R. Miller
- & J. Keith Joung
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Article |
High-fidelity Cas13 variants for targeted RNA degradation with minimal collateral effects
Several engineered Cas13 variants achieve targeted RNA degradation with minimal collateral effects.
- Huawei Tong
- , Jia Huang
- & Hui Yang
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Article
| Open Access
Logic-gated antibody pairs that selectively act on cells co-expressing two antigens
Antibody pairs are made to act selectively on cells co-expressing two targets by engineering their Fc domains.
- Simone C. Oostindie
- , Derek A. Rinaldi
- & Rob N. de Jong
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News & Views |
A new route to vaccines using PROTACs
An influenza vaccine is created by attenuating the live virus through targeted proteolysis.
- Brad Gilbertson
- & Kanta Subbarao
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Article
| Open Access
The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants
Multiple variants of SARS-CoV-2 are inhibited by a trispecific DARPin.
- Sylvia Rothenberger
- , Daniel L. Hurdiss
- & Jakob Trimpert
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Research Briefing |
Plant hormone sensors as scaffolds for biosensor design
Most plant hormone sensors, including the abscisic acid receptor PYR1, function through chemically induced dimerization. Using computationally designed libraries of PYR1, we created high-affinity receptors for 21 structurally diverse ligands, setting the stage for large-scale small-molecule biosensor development
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Article
| Open Access
Rapid biosensor development using plant hormone receptors as reprogrammable scaffolds
Biosensors are developed from malleable hormone receptors.
- Jesús Beltrán
- , Paul J. Steiner
- & Timothy A. Whitehead
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Article |
A red light–responsive photoswitch for deep tissue optogenetics
A photoswitch based on a bacterial phytochrome enables optogenetic manipulations using red light.
- Yuto Kuwasaki
- , Kazushi Suzuki
- & Moritoshi Sato
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Brief Communication
| Open Access
Thermodynamically coupled biosensors for detecting neutralizing antibodies against SARS-CoV-2 variants
SARS-CoV-2 neutralizing antibodies are readily detected with a biosensor.
- Jason Z. Zhang
- , Hsien-Wei Yeh
- & David Baker
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Article |
Engineered circular ADAR-recruiting RNAs increase the efficiency and fidelity of RNA editing in vitro and in vivo
Circular ADAR-recruiting RNAs improve RNA editing in vitro and in a mouse disease model.
- Zongyi Yi
- , Liang Qu
- & Wensheng Wei
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Article |
Learning protein fitness models from evolutionary and assay-labeled data
A simple machine learning algorithm combines evolutionary and experimental data for improved protein fitness prediction.
- Chloe Hsu
- , Hunter Nisonoff
- & Jennifer Listgarten
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Article |
Optogenetic control of RNA function and metabolism using
engineered light-switchable RNA-binding proteins
Photoswitchable RNA-binding proteins enable the spatiotemporal control of RNA function.
- Renmei Liu
- , Jing Yang
- & Yi Yang
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Article
| Open Access
Genetically encoded photo-switchable molecular sensors for optoacoustic and super-resolution imaging
Calcium and other analytes can be imaged at super-resolution and in vivo with photo-switchable sensors.
- Kanuj Mishra
- , Juan Pablo Fuenzalida-Werner
- & Andre C. Stiel
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Letter |
Engineering luminescent biosensors for point-of-care SARS-CoV-2 antibody detection
A rapid, split luciferase test for SARS-CoV-2 antibodies in blood and saliva compatible with lyophilization and use in low-resource settings.
- Susanna K. Elledge
- , Xin X. Zhou
- & James A. Wells
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Article |
A near-infrared genetically encoded calcium indicator for in vivo imaging
A near-infrared fluorescent calcium indicator can be combined with other optogenetic tools in vivo without spectral crosstalk.
- Anton A. Shemetov
- , Mikhail V. Monakhov
- & Vladislav V. Verkhusha
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Brief Communication |
Isolating live cell clones from barcoded populations using CRISPRa-inducible reporters
Cell clones in lineage-tracing studies can be isolated for functional experiments.
- Christian Umkehrer
- , Felix Holstein
- & Anna C. Obenauf
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Letter |
CRISPR C-to-G base editors for inducing targeted DNA transversions in human cells
A new base editor enables the creation of C-to-G base changes in human cells.
- Ibrahim C. Kurt
- , Ronghao Zhou
- & J. Keith Joung
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Brief Communication |
A dual-deaminase CRISPR base editor enables concurrent adenine and cytosine editing
A base editor that concurrently modifies both adenine and cytosine broadens the potential applications of base editing.
- Julian Grünewald
- , Ronghao Zhou
- & J. Keith Joung
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Brief Communication |
An engineered ScCas9 with broad PAM range and high specificity and activity
A hybrid CRISPR–Cas9 variant is able to specifically and efficiently target a larger proportion of the genome.
- Pranam Chatterjee
- , Noah Jakimo
- & Joseph Jacobson
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Article
| Open Access
A male-biased sex-distorter gene drive for the human malaria vector Anopheles gambiae
A sex-distorter gene drive causes population collapse in the malaria mosquito.
- Alekos Simoni
- , Andrew M. Hammond
- & Andrea Crisanti
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Article |
Directed evolution of adenine base editors with increased activity and therapeutic application
Adenine base editors are evolved to be more efficient and more compatible with Cas9 variants.
- Nicole M. Gaudelli
- , Dieter K. Lam
- & Giuseppe Ciaramella
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Letter |
Massively parallel Cas13 screens reveal principles for guide RNA design
Design of optimal guide RNAs for Cas13d-mediated RNA knockdown is enabled by computational modeling of large-scale screening data.
- Hans-Hermann Wessels
- , Alejandro Méndez-Mancilla
- & Neville E. Sanjana
Making genome editing a success story in Africa