CRISPR-Cas systems articles within Nature Communications

Featured

  • Article
    | Open Access

    SpCas9 off-targets are a safety concern. Here the authors report a cleavage rule that governs the on-target and off-target cleavage of increased(/high)-fidelity SpCas9 variants: the variants have differences in fidelity small enough to comprise an optimal variant for each target, irrespective of its cleavability ranking.

    • Péter István Kulcsár
    • , András Tálas
    •  & Ervin Welker

  • Article
    | Open Access

    Gene editing is still hampered by unintended genomic alterations. Here the authors propose a method for correcting heterozygous mutations that employs multiple nicks induced by Cas9 nickase and the homologous chromosome as an endogenous repair template (NICER): this rarely induces unintended genomic alterations.

    • Akiko Tomita
    • , Hiroyuki Sasanuma
    •  & Shinichiro Nakada

  • Article
    | Open Access

    CRISPRi is used for gene silencing in mammalian cells. Here the authors report a gene-suppression/activation strategy using active Cas9 complexed with truncated gRNAs (tgCRISPRi/a) without causing DNA cleavage: they use this to repress or activate expression of several target genes throughout somatic tissues in Drosophila melanogaster.

    • Ankush Auradkar
    • , Annabel Guichard
    •  & Ethan Bier

  • Article
    | Open Access

    TadA deaminases widely used in many base editors lack post-translational control in cells. Here the authors report a split adenine base editor (sABE) using chemically induced dimerisation (CID) to control the catalytic activity of TadA8e and show this can be used for PCSK9 gene editing in the mouse liver.

    • Hongzhi Zeng
    • , Qichen Yuan
    •  & Xue Gao

  • Article
    | Open Access

    Small Cas enzymes are required for therapeutic use. Here the authors report an Interaction, Dynamics and Conservation (IDC) strategy for protein miniaturisation and use this to generate five compact variants of Cas13 based on a combination of IDC strategy and AlphaFold2.

    • Feiyu Zhao
    • , Tao Zhang
    •  & Zhanjun Li

  • Article
    | Open Access

    Current bacterial sgRNA activity models struggle with accurate predictions and generalizations. Here the authors report crisprHAL, a machine learning architecture that can be trained on existing datasets, and shows good sgRNA activity prediction accuracy can generalize predictions to different bacteria.

    • Dalton T. Ham
    • , Tyler S. Browne
    •  & David R. Edgell

  • Article
    | Open Access

    Cas12a is widely used in diagnostic platforms. Here the authors show that Cas12a can be programmed to directly detect RNA substrates, this is due to the 3’-end of the crRNA tolerating both RNA and DNA substrates: they use this to report a method, SAHARA, to detect RNA sequences.

    • Santosh R. Rananaware
    • , Emma K. Vesco
    •  & Piyush K. Jain

  • Article
    | Open Access

    Base editors can induce unwanted off-target effects. Here the authors design libraries of gRNA-off-target pairs and perform a screen to obtain editing efficiencies for ABE and CBE: they use the datasets to train DL models (ABEdeepoff and CBEdeepoff) which can predict mutation tolerance at potential off-targets.

    • Chengdong Zhang
    • , Yuan Yang
    •  & Yongming Wang

  • Article
    | Open Access

    Low efficiency of target DNA integration remains a challenge in genome engineering. Here the authors perform large-scale compound library and genetic screens to identify targets that enhance gene editing: they see that combined DNA-PK and Polϴ inhibition with potent compounds increases editing efficiency and precision.

    • Sandra Wimberger
    • , Nina Akrap
    •  & Marcello Maresca

  • Article
    | Open Access

    Chronic wounds impose a significant burden to a broad patient population. Here, the authors use CRISPR/Cas9 to enhance the regenerative capacity of dendritic cells by knocking out the gene Ndrg2, and show that seeding these engineered dendritic cells on hydrogels constitutes an effective therapy for chronic wounds in diabetic and non-diabetic conditions.

    • Dominic Henn
    • , Dehua Zhao
    •  & Geoffrey C. Gurtner

  • Article
    | Open Access

    CRISPR-Cas immunity systems safeguard prokaryotic genomes by inhibiting the invasion of mobile genetic elements. Here, the authors show that insertion sequences can efficiently insert into cas genes, thus inactivating CRISPR defenses and increasing bacterial susceptibility to foreign DNA invasion.

    • Yong Sheng
    • , Hengyu Wang
    •  & Qianjin Kang

  • Article
    | Open Access

    ON-target genotoxicity in gene editing is generally underestimated. Here the authors report Fluorescence-Assisted Megabase-scale Rearrangements Detection (FAMReD) systems to detect and characterize rare large loss of heterozygosity: they show that ON-target genotoxicity can be prevented by p53 and cell cycle arrest.

    • G. Cullot
    • , J. Boutin
    •  & A. Bedel

  • Article
    | Open Access

    The details of CRISPR-Cas target search are unresolved. Here the authors analyse the target search process of the Type I CRISPR-Cas complex Cascade: they show that target search and target recognition are tightly linked, and DNA supercoiling and limited 1D diffusion play a role.

    • Pierre Aldag
    • , Marius Rutkauskas
    •  & Ralf Seidel

  • Article
    | Open Access

    The role of mutations within long noncoding RNAs (lncRNAs) exons on tumour cell fitness remains to be explored. Here, the authors investigate the landscape of driver lncRNAs in primary and metastatic samples and validate the functional significance of single nucleotide variants in the NEAT1 oncogene in vitro and in vivo.

    • Roberta Esposito
    • , Andrés Lanzós
    •  & Rory Johnson

  • Article
    | Open Access

    Retrotransposons replicate their genetic information through target-primed reverse transcription (TPRT). Here the authors report a template-jumping prime editor (TJ-PE) to act similarly to TPRT and achieve insertions of large DNA fragments at endogenous sites: they rewrite a mutated exon in the mouse liver.

    • Chunwei Zheng
    • , Bin Liu
    •  & Wen Xue

  • Article
    | Open Access

    Concentrative nucleoside transporters (CNTs) are cellular nucleoside influx systems, but their in vivo roles are poorly defined. By generating CNT1 knockout (KO) mice, here the authors show a role of CNT1 in the renal reabsorption of endogenous and synthetic nucleosides.

    • Avinash K. Persaud
    • , Matthew C. Bernier
    •  & Rajgopal Govindarajan

  • Article
    | Open Access

    Limited work has been done on concurrent C-to-G and A-to-G base editing. Here the authors test how a number of chromatin-associated factors affect base editing and show that HMGN1 enhanced the efficiency; by fusing HMGN1 to GBE and ABE they develop a CRISPR-based dual-function A-to-G and C-to-G base editor (GGBE).

    • Chao Yang
    • , Zhenzhen Ma
    •  & Xueli Zhang

  • Article
    | Open Access

    The authors demonstrate efficient and direct correction of the DNA mutation causing Haemoglobin E β-thalassaemia with CRISPR Cas9 base editors. The work includes profiling of off-target effects using deep neural networks.

    • Mohsin Badat
    • , Ayesha Ejaz
    •  & James O. J. Davies

  • Article
    | Open Access

    CRISPR-regulated toxin-antitoxin (CreTA), safeguards CRISPR-Cas immune systems. Here the authors characterize a bacterial CreTA and use this to generate a proof-of-concept antimicrobial strategy, ATTACK, which associates TA and CRISPR-Cas to kill multidrug resistant pathogens.

    • Rui Wang
    • , Xian Shu
    •  & Ming Li

  • Article
    | Open Access

    Cas9 nickases (nCas9s) produce nicks or single-strand breaks in the DNA. Here the authors analyse the on- and off-target nicks generated by these nickases, and show that nCas9 (H840A) but not nCas9 (D10A) can cleave both strands and produce unwanted DNA double-strand breaks.

    • Jaesuk Lee
    • , Kayeong Lim
    •  & Jin-Soo Kim

  • Comment
    | Open Access

    We address a controversy over use of the term “gene drive” to include both natural and synthetic genetic elements that promote their own transmission within a population, arguing that this broad definition is both practical and has advantages for risk analysis.

    • Stephanie L. James
    • , David A. O’Brochta
    •  & Omar S. Akbari

  • Article
    | Open Access

    Nucleic acid sensing involving CRISPR technologies is powerful but has certain limitations, such as PAM sequence requirements and limited multiplexing. Here, authors report a CRISPR-based barcoding technology which enables multiple outputs from any target sequence, based on cis- and trans-cleavage.

    • Margot Karlikow
    • , Evan Amalfitano
    •  & Keith Pardee

  • Article
    | Open Access

    DNA repair in response to DSBs in the preimplantation embryo is hard to analyze. Here the authors show that over 25% of pre-existing heterozygous loci in control single blastomere samples appeared as homozygous after whole genome amplification, therefore, they validated gene editing seen in human embryos in ESCs.

    • Dan Liang
    • , Aleksei Mikhalchenko
    •  & Shoukhrat Mitalipov

  • Article
    | Open Access

    There is a low efficiency of A-to-G base conversion in at specific positions using base editors. Here the authors fuse ABE8e with the Rad51 DNA-binding domain to generate a hyperactive ABE allowing improved A-to-G editing efficiency at the region proximal to the PAM and improved simultaneous A/C conversion efficiency.

    • Niannian Xue
    • , Xu Liu
    •  & Xiaohui Zhang

  • Article
    | Open Access

    Delivery of immune therapy drugs to tumours might be hampered by their limited bioavailability and the difficulty of targeting complex exogenous compounds. Here authors trigger immunologic cell death, via activating tumour-cell-intrinsic pathways via CRISPR-based nanotechnology to enable efficient anti-tumour immune response in mouse models of melanoma.

    • Ning Wang
    • , Chao Liu
    •  & Changyang Gong

  • Article
    | Open Access

    Genome editing in bacteria normally requires efficient recombination and high transformation efficiencies, which often isn’t. Here the authors report that systematically attenuating DNA targeting activity enables RecA-mediated repair in different bacteria, allowing chromosomal cleavage to drive editing.

    • Daphne Collias
    • , Elena Vialetto
    •  & Chase L. Beisel

  • Article
    | Open Access

    Induced pluripotent stem cell (iPSC) reprogramming is inherently inefficient. Here the authors identify 24 reprogramming roadblock genes through a CRISPR/Cas9-mediated genome-wide knockout screen including a KRAB-ZFP Zfp266, knockout of which consistently enhances murine iPSC generation.

    • Daniel F. Kaemena
    • , Masahito Yoshihara
    •  & Keisuke Kaji

  • Article
    | Open Access

    CRISPR/Cas9-based homing gene drives have emerged as a potential new approach to mosquito control. Here the authors use transgenic lines with germline-specific regulatory elements to express Cas9 and achieve up to 94% inheritance bias, closing the gap between A. aegyptidrives and the highly efficient drives observed in Anopheles species.

    • Michelle A. E. Anderson
    • , Estela Gonzalez
    •  & Luke Alphey

  • Article
    | Open Access

    Strategies to improve the specificity of nuclease-based prime editor (PEn) are needed. Here the authors report a 53BP1-inhibitory ubiquitin variant-assisted PEn platform (uPEn) to inhibit NHEJ and enable precise prime editing for generation of insertions, deletions and replacements.

    • Xiangyang Li
    • , Guiquan Zhang
    •  & Xingxu Huang

  • Review Article
    | Open Access

    CRISPR-Cas tools have shown exceptional promise in genome engineering over the past decade. Here the authors review the development of CRISPR-Cas9/Cas12/Cas13 nucleases, DNA base editors, prime editors, and RNA base editors, as well as their editing precision, off-target effects, and clinical considerations.

    • Jianli Tao
    • , Daniel E. Bauer
    •  & Roberto Chiarle

  • Article
    | Open Access

    Here, Liao and colleagues apply adenine base editor ABE8e and its PAM-less variant ABE8e-SpRY to β-thalassemia patient hematopoietic stem cells in the form of ribonucleoprotein complexes, resulting in efficient long-term editing and β-thalassemia alleviation.

    • Jiaoyang Liao
    • , Shuanghong Chen
    •  & Yuxuan Wu

  • Article
    | Open Access

    CRISPR-based gene-drives can carry the Cas9 and guide RNA (gRNA) components in a single-linked cassette or in separate elements inserted into different genomic loci. Here the authors genetically transform and compare full versus split drives, with the former performing less efficiently than predicted.

    • Gerard Terradas
    • , Jared B. Bennett
    •  & Ethan Bier

  • Article
    | Open Access

    The effect of sequence polymorphisms on recombination is not fully understood. Here, the authors develop the seed-typing method to map crossovers (COs) by sequencing and show that COs occur preferentially within polymorphic hotspots and that this effect depends on the mismatch repair gene MSH2 in Arabidopsis.

    • Maja Szymanska-Lejman
    • , Wojciech Dziegielewski
    •  & Piotr A. Ziolkowski

  • Article
    | Open Access

    Efferocytosis describes the engulfment and clearance of apoptotic cells by phagocytes. Here the authors identify in primary mouse macrophage WDFY3 as a regulator for efferocytosis, in which c-terminal WDFY3 is sufficient to modulate degradation while full-length WDFY3 is required to modulate the uptake of apoptotic cells.

    • Jianting Shi
    • , Xun Wu
    •  & Hanrui Zhang

  • Article
    | Open Access

    It is still a challenge to accurately identify off-target endonuclease edits. Here the authors report PEAC-seq using a Prime Editor to insert a tag to the editing sites and enrich the tagged regions with site-specific primers for sequencing: they show that PEAC-seq could identify DNA translocations.

    • Zhenxing Yu
    • , Zhike Lu
    •  & Lijia Ma

  • Article
    | Open Access

    Bacteria are equipped with diverse immune strategies to fight bacteriophage infections, including restriction nucleases, abortive infection and CRISPR-Cas systems. Here, Arias et al. use mathematical models of immune responses in individual bacterial cells to highlight the importance of the timing and coordination of different antiviral systems, and present hypotheses that may inspire future research.

    • Clemente F. Arias
    • , Francisco J. Acosta
    •  & Cristina Fernández-Arias

Browse broader subjects

Browse narrower subjects

Browse CRISPR-Cas systems across other nature.com journals