Featured
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Near-cognate tRNAs increase the efficiency and precision of pseudouridine-mediated readthrough of premature termination codons
Disease-related premature stop codons are efficiently corrected by harnessing near-cognate tRNAs.
- Nan Luo
- , Qiang Huang
- & Chengqi Yi
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Article
| Open AccessActivation of recombinases at specific DNA loci by zinc-finger domain insertions
Recombinases fused with zinc-finger domains are active only when bound to their DNA targets.
- Liliya Mukhametzyanova
- , Lukas Theo Schmitt
- & Frank Buchholz
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Article
| Open AccessIn vivo human T cell engineering with enveloped delivery vehicles
Cell-specific molecular delivery with enveloped delivery vehicles enables genome editing ex vivo and in vivo.
- Jennifer R. Hamilton
- , Evelyn Chen
- & Jennifer A. Doudna
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Article |
Prime editing using CRISPR-Cas12a and circular RNAs in human cells
Prime editing with CRISPR-Cas12a broadens targeting scope and enables multiplexing.
- Ronghong Liang
- , Zixin He
- & Caixia Gao
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Brief Communication |
Delivery of a sebum modulator by an engineered skin microbe in mice
An engineered skin microbe produces a therapeutic molecule that reduces sebum in mice.
- Nastassia Knödlseder
- , María-José Fábrega
- & Marc Güell
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Article
| Open AccessEngineered virus-like particles for transient delivery of prime editor ribonucleoprotein complexes in vivo
Delivery of prime editors in vivo is improved using virus-like particles.
- Meirui An
- , Aditya Raguram
- & David R. Liu
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Article |
Glycosylase-based base editors for efficient T-to-G and C-to-G editing in mammalian cells
Base editors lacking a deaminase improve thymine and cytosine conversion.
- Lijun Ye
- , Dongdong Zhao
- & Changhao Bi
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Correspondence |
A new chance for genome editing in Europe
- Hervé Vanderschuren
- , Patience Chatukuta
- & Devang Mehta
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Article |
High-efficiency transgene integration by homology-directed repair in human primary cells using DNA-PKcs inhibition
A small molecule enhances targeted gene integration at therapeutically relevant loci in human primary cells.
- Sridhar Selvaraj
- , William N. Feist
- & Matthew H. Porteus
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Article |
Prediction of on-target and off-target activity of CRISPR–Cas13d guide RNAs using deep learning
A machine learning model predicts on-target and off-target activity of Cas13d in human cells.
- Hans-Hermann Wessels
- , Andrew Stirn
- & Neville E. Sanjana
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Article |
Evolutionary mining and functional characterization of TnpB nucleases identify efficient miniature genome editors
Compact genome editors were discovered by mining a transposon library.
- Guanghai Xiang
- , Yuanqing Li
- & Haoyi Wang
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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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Research Briefing |
CRISPR-free, strand-selective mitochondrial DNA base editing using a nickase
The fusion of a programmable transcription-activator-like effector (TALE) protein with a nickase, in conjunction with a deaminase, enables efficient and strand-selective DNA base editing. This approach has the potential to advance our understanding and treatment of diseases associated with mutations in the mitochondrial or nuclear genome.
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Article
| Open AccessStrand-selective base editing of human mitochondrial DNA using mitoBEs
Mitochondrial point mutations are corrected in human cells using a transcription activator-like effector (TALE)-based system.
- Zongyi Yi
- , Xiaoxue Zhang
- & Wensheng Wei
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Article |
Deep learning models to predict the editing efficiencies and outcomes of diverse base editors
The best base editor for specific applications is predicted with a deep learning model.
- Nahye Kim
- , Sungchul Choi
- & Hyongbum Henry Kim
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Article |
A prime editor mouse to model a broad spectrum of somatic mutations in vivo
Prime-editing mouse models enable the study of specific cancer mutations in vivo.
- Zackery A. Ely
- , Nicolas Mathey-Andrews
- & Tyler Jacks
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Article
| Open AccessEfficient prime editing in mouse brain, liver and heart with dual AAVs
Prime editors are efficiently delivered to mouse organs with AAV vectors.
- Jessie R. Davis
- , Samagya Banskota
- & David R. Liu
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Article |
Efficient engineering of human and mouse primary cells using peptide-assisted genome editing
Peptide-assisted genome editing enables efficient single and multiplex editing in hematopoietic cells.
- Zhen Zhang
- , Amy E. Baxter
- & Junwei Shi
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Brief Communication
| Open AccessInterstrand crosslinking of homologous repair template DNA enhances gene editing in human cells
The efficiency of homologous recombination is increased by crosslinking template DNA.
- Hannah I. Ghasemi
- , Julien Bacal
- & Chris D. Richardson
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Article
| Open AccessEngineered human hepatocyte organoids enable CRISPR-based target discovery and drug screening for steatosis
Organoid models of early liver disease aid target discovery and drug screening.
- Delilah Hendriks
- , Jos F. Brouwers
- & Hans Clevers
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Article
| Open AccessPrediction 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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Research Briefing |
CLASH enables large-scale parallel knock-in for cell engineering
CLASH is a CRISPR-based platform that enables the parallel knock-in via homology-directed repair of a large pool of transgene variants encoded in adeno-associated virus vectors. CLASH can be applied to the systematic and unbiased selection of favorable features in T cells and, in principle, other cell types.
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Article |
Predicting prime editing efficiency and product purity by deep learning
The design of prime editing guide RNAs is optimized by deep learning.
- Nicolas Mathis
- , Ahmed Allam
- & Gerald Schwank
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News & Views |
Novel recombinases for large DNA insertions
Bioinformatic mining and engineering of serine recombinases yields improved genome editing tools.
- George D. Lampe
- & Samuel H. Sternberg
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Article |
Re-engineering the adenine deaminase TadA-8e for efficient and specific CRISPR-based cytosine base editing
Improved cytosine base editors are created by repurposing an adenine deaminase.
- Liang Chen
- , Biyun Zhu
- & Dali Li
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Article
| Open AccessEvolution of an adenine base editor into a small, efficient cytosine base editor with low off-target activity
Improved cytosine base editors are generated by phage-assisted evolution of a deoxyadenosine deaminase.
- Monica E. Neugebauer
- , Alvin Hsu
- & David R. Liu
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Article
| Open AccessPrecision 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
| Open AccessSystematic discovery of recombinases for efficient integration of large DNA sequences into the human genome
Screening recombinases identifies tools for inserting large sequences into the human genome.
- Matthew G. Durrant
- , Alison Fanton
- & Patrick D. Hsu
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Brief Communication
| Open AccessA competitive precision CRISPR method to identify the fitness effects of transcription factor binding sites
A competitive CRISPR method discovers targets and phenotypic effects of the MYC oncogene.
- Päivi Pihlajamaa
- , Otto Kauko
- & Jussi Taipale
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Article
| Open AccessHigh-throughput continuous evolution of compact Cas9 variants targeting single-nucleotide-pyrimidine PAMs
Directed evolution creates new compact Cas9 variants that target most single pyrimidine nucleotide PAMs.
- Tony P. Huang
- , Zachary J. Heins
- & David R. Liu
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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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Matters Arising |
Assessing the efficiency of Verily’s automated process for production and release of male Wolbachia-infected mosquitoes
- Jérémy Bouyer
- , Hamidou Maiga
- & Marc J. B. Vreysen
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News & Views |
Pathogenic or benign?
CRISPR base- and prime-editing pooled screens reveal the function of genetic variants at unprecedented resolution.
- Peter P. Du
- , Katherine Liu
- & Gaelen T. Hess
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Article |
A split prime editor with untethered reverse transcriptase and circular RNA template
A split prime editor simplifies delivery.
- Bin Liu
- , Xiaolong Dong
- & Erik J. Sontheimer
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Article
| Open AccessDevelopment of spirulina for the manufacture and oral delivery of protein therapeutics
Spirulina is used to manufacture a therapeutic antibody against campylobacter.
- Benjamin W. Jester
- , Hui Zhao
- & James Roberts
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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 |
Efficient in vitro and in vivo RNA editing via recruitment of endogenous ADARs using circular guide RNAs
Circular guide RNAs boost the efficiency of RNA editing with endogenous ADARs.
- Dhruva Katrekar
- , James Yen
- & Prashant Mali
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Article |
Programmable deletion, replacement, integration and inversion of large DNA sequences with twin prime editing
Prime editing of large DNA sequences is achieved with two pegRNAs and site-specific recombinases.
- Andrew V. Anzalone
- , Xin D. Gao
- & David R. Liu
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News & Views |
Improving CRISPR tools by elucidating DNA repair
Genome-editing tools are optimized by identifying genes that affect DNA repair.
- Jung Min Lim
- & Hyongbum Henry Kim
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Article |
Precise genomic deletions using paired prime editing
Paired prime editing is used to precisely delete genomic sequences up to 10 kb.
- Junhong Choi
- , Wei Chen
- & Jay Shendure
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Article |
Deletion and replacement of long genomic sequences using prime editing
Prime editing is expanded to deletions and replacements of genomic sequences of up to 10 kb.
- Tingting Jiang
- , Xiao-Ou Zhang
- & Wen Xue
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Article |
Engineered pegRNAs improve prime editing efficiency
Stabilizing pegRNAs with 3′ RNA structures increases prime editing efficiency.
- James W. Nelson
- , Peyton B. Randolph
- & David R. Liu
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Article |
A small and highly sensitive red/far-red optogenetic switch for applications in mammals
Highly sensitive photoswitchable dimerizer enables the control of biological processes with red light in mammals.
- Yang Zhou
- , Deqiang Kong
- & Haifeng Ye
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Article |
Adenine base editor engineering reduces editing of bystander cytosines
Engineered variants of adenine base editors have reduced cytosine base editing or a specific C-to-G base editing activity.
- You Kyeong Jeong
- , SeokHoon Lee
- & Sangsu Bae
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Article |
Efficient C•G-to-G•C base editors developed using CRISPRi screens, target-library analysis, and machine learning
Efficiency of transversion base editing is increased by matching a set of base editors to target sequences.
- Luke W. Koblan
- , Mandana Arbab
- & David R. Liu
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Article
| Open AccessIn vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels
Base editors are effective and safe for cholesterol reduction in non-human primates.
- Tanja Rothgangl
- , Melissa K. Dennis
- & Gerald Schwank
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Article |
Profiling the genetic determinants of chromatin accessibility with scalable single-cell CRISPR screens
The effects of gene knockouts on chromatin accessibility are measured with single-cell CRISPR screens.
- Noa Liscovitch-Brauer
- , Antonino Montalbano
- & Neville E. Sanjana