CRISPR-Cas systems articles within Nature Communications

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  • Article
    | Open Access

    Cas12i is a genome editing platform with compact size that fits in AAV vector with short 43-mer gRNA, absence of tracrRNA, ability to process pre-crRNA, and high specificity. Here the authors present an unbiased mutational scanning approach to engineer Cas12i, which shows low activity in mammalian cells, and identify single substitutions that significantly improve indel activity.

    • Colin McGaw
    • , Anthony J. Garrity
    •  & Shaorong Chong

  • Article
    | Open Access

    Current base- and prime-editing technologies lack efficient strategies to edit multiple genomic loci simultaneously, limiting their applications in complex genomics and polygenic diseases. Here the authors describe drive-and-process CRISPR array architectures for multiplex base-editing and multiplex prime-editing in human cells.

    • Qichen Yuan
    •  & Xue Gao

  • Article
    | Open Access

    A major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here the authors show that CRISPR-Cas13d can be used as a broad-spectrum antiviral to inhibit human coronaviruses, including new SARS-CoV-2 variants, combined with small molecule drugs for an enhanced antiviral effect in human primary cells.

    • Leiping Zeng
    • , Yanxia Liu
    •  & Lei S. Qi

  • Article
    | Open Access

    PAM requirement is a constraint for genome editing but this has been circumvented by engineered Cas9 nucleases as SpG and SpRY recognizing minimal PAM sequences. Here, the authors validate and optimize SpG and SpRY in vivo expanding the targeting landscape in animals.

    • Jeremy Vicencio
    • , Carlos Sánchez-Bolaños
    •  & Miguel A. Moreno-Mateos

  • Article
    | Open Access

    Gene circuits must resist epigenetic silencing for reliable therapeutic applications. Here the authors develop an RNA-level regulation platform using CRISPR endoRNases that is modular, scalable, and more stable than traditional transcriptional versions.

    • Breanna DiAndreth
    • , Noreen Wauford
    •  & Ron Weiss

  • Article
    | Open Access

    Here the authors perform a genome-wide CRISPR-Cas9 knockout screen to systematically identify and characterize essential and growth-restricting genes in human trophoblast cells. They identify TEAD1 as a key regulator that plays an important role in the specification, maintenance, and differentiation of the human trophoblast lineage by modulating chromatin architecture and gene expression.

    • Chen Dong
    • , Shuhua Fu
    •  & Thorold W. Theunissen

  • Article
    | Open Access

    CRISPR gene drives are genetic elements capable of quickly spreading through populations and they offer promising solutions for curbing the spread of vector-borne diseases and controlling crop pest and invasive species populations. Here the authors present a method for overcoming resistance alleles “double-tap,” that encodes additional gRNAs in the gene drive that target the most common generated resistance alleles.

    • Alena L. Bishop
    • , Víctor López Del Amo
    •  & Valentino M. Gantz

  • Article
    | Open Access

    Programmable double-strand DNA breaks (DSBs) can be harnessed for precision genome editing through manipulation of the homology-directed repair (HDR) pathway. Here the authors report the development of the double tap - double tap implements secondary gRNAs which target Cas9 to common indel sequences and provides a second chance at HDR.

    • Zsolt Bodai
    • , Alena L. Bishop
    •  & Alexis C. Komor

  • Article
    | Open Access

    Combinatorial CRISPR screens can be utilized to identify genetic interactions and functional redundancies of multiple genes. Here, the authors benchmark ten digenic CRISPR technologies and identify novel Cas9 tracrRNA combinations that show superior performance.

    • Ruitong Li
    • , Olaf Klingbeil
    •  & William R. Sellers

  • Article
    | Open Access

    Here, Mac Kain and Maarifi et al. perform a functional CRISPR/Cas9 screen to identify SARS-CoV-2 restriction factors in A549 cells. They identify DAXX, a scaffold protein of nuclear bodies with diverse functions, that has anti-viral activity post SARS-CoV-2 entry, while SARS-CoV-2 has evolved a mechanism to counteract its action via PLpro-mediated proteasomal degradation.

    • Alice Mac Kain
    • , Ghizlane Maarifi
    •  & Ferdinand Roesch

  • Article
    | Open Access

    Here, Israeli and Finkel et al. perform genome-wide CRISPR knockout screens to identify host factors required for the infection with SARS-CoV-2 and two additionally variants of concern, Alpha and Beta, unveiling shared and differential host pathways required by the variants, and demonstrate GATA6 is critical for SARS-CoV-2 viral entry through modulation of ACE2 expression.

    • Ma’ayan Israeli
    • , Yaara Finkel
    •  & Adi Bercovich-Kinori

  • Article
    | Open Access

    Targeting integrin-mediated retention of malignant B cells in their protective microenvironment is an efficacious treatment for lymphoma and leukemia. Here, the authors present an unbiased loss-of-adhesion CRISPR screening method, identifying therapeutic targets for these B-cell malignancies.

    • Martin F. M. de Rooij
    • , Yvonne J. Thus
    •  & Marcel Spaargaren

  • Article
    | Open Access

    RNA modifications, including N6-methyladenosine (m6A), have been reported to regulate fundamental RNA processes and properties, and directly linked to various human diseases. Here, the authors develop a chemically inducible and reversible RNA m6A modification editing platform integrating chemically induced proximity (CIP) and CRISPR methods.

    • Huaxia Shi
    • , Ying Xu
    •  & Fu-Sen Liang

  • Article
    | Open Access

    Phages use anti-CRISPR proteins (Acrs) to counteract the bacterial CRISPR-Cas systems. Here, the authors characterize AcrIF24, which functions as an Aca (Acr-associated) to repress and regulate its own transcription, dimerizes the Csy complex, blocks the hybridization of target DNA, and tethers non-sequence-specific DNA to the Csy complex.

    • Lingguang Yang
    • , Laixing Zhang
    •  & Yue Feng

  • Article
    | Open Access

    The prime editors (PEs) have shown great promise for precise genome modification. Here the authors place a stabilizing viral xrRNA motif to the 3′ of pegRNAs to enhance editing efficiencies.

    • Guiquan Zhang
    • , Yao Liu
    •  & Jianghuai Liu

  • Article
    | Open Access

    Prime editors can mediate all twelve types of base substitutions and small insertions or deletions in living cells but its efficiency remains low. Here the authors introduce same-sense mutations into pegRNAs to increase base-editing efficiency and the pegRNA secondary structure was altered to increase indel-editing efficiency.

    • Xiaosa Li
    • , Lina Zhou
    •  & Jia Chen

  • Article
    | Open Access

    Base editors are genome engineering tools that can generate nucleotide substitutions without introducing double-stranded breaks. Here the authors show that a phage-derived peptidyl CRISPR inhibitor can be employed to modulate the activity and targeting scope of CRISPR base editor for precision base editing applications.

    • Kun Jia
    • , Yan-ru Cui
    •  & Jia Liu

  • Article
    | Open Access

    Gene editing tools have tremendous potential for biomedical and basic research. Here the authors report a Cas9 from Faecalibaculum rodentium (FrCas9) that achieves efficient and specific gene editing in human cells with a NNTA palindrome PAMs for targeting optimal sites at TATA-boxes to enhance CRISPRa/i screening.

    • Zifeng Cui
    • , Rui Tian
    •  & Zheng Hu

  • Article
    | Open Access

    Cas9 off-target sites can be predicted by many bioinformatics tools. Here the authors present low complexity mechanistic model that characterizes SpCas9 kinetics in free-energy terms, allowing quantitative prediction of off-target activity in bulk-biochemistry, single molecule, and whole-genome profiling experiments.

    • Behrouz Eslami-Mossallam
    • , Misha Klein
    •  & Martin Depken

  • Article
    | Open Access

    Numerous rationally-designed and directed-evolution variants of SpCas9 have been reported to expand the utility of CRISPR technology. Here the authors make comparisons of numerous Cas9 variants, nominate options for base editing screens with denser coverage with A>G and C>T base editing screens and identify loss-of-function mutations in BRCA1 and Venetoclax-resistant mutations in BCL2.

    • Annabel K. Sangree
    • , Audrey L. Griffith
    •  & John G. Doench

  • Article
    | Open Access

    The off-target effects of CRISPR-Cas9 are thought to be mediated by its cognate guide RNA. Here the authors show that Cas9 independently interacts with the human transcriptome, correlating with elevated RNA editing even under guide RNA co-expression.

    • Aaron A. Smargon
    • , Assael A. Madrigal
    •  & Gene W. Yeo

  • Article
    | Open Access

    While prime editing is a promising technique, some genomic sites remain difficult to edit. Here the authors present fluoPEER, fluorescent prime editing and enrichment reporter, to rank the efficiency of pegRNAs and prime editor variants.

    • I. F. Schene
    • , I. P. Joore
    •  & S. A. Fuchs

  • Article
    | Open Access

    Pre-existing antibodies against Cas9 proteins represent a potential issue for gene therapies, including those targeting the eye. Here the authors assess the presence of intraocular antibodies, and show that Cas9 antibodies were prevalent in human serum but not the eye, unless prior bacterial infection occurred.

    • Marcus A. Toral
    • , Carsten T. Charlesworth
    •  & Vinit B. Mahajan

  • Article
    | Open Access

    The contractile properties of adult myofibers are shaped by their Myosin heavy chain isoform content. Here the authors show that a super enhancer controls the spatiotemporal expression of the genes at the fast myosin heavy chain locus by DNA looping and that this expression profile is recapitulated in a rainbow transgenic mouse model of the locus.

    • Matthieu Dos Santos
    • , Stéphanie Backer
    •  & Pascal Maire

  • Article
    | Open Access

    T follicular helper (Tfh) and T help type 1 (Th1) cells both arise from naïve CD4 T cells, but detailed knowledge of their differentiation remains incomplete. Here the authors pursue an in vivo CRISPR screen to identify genes, focusing on druggable targets, regulating Tfh versus Th1 to provide a resource for related studies, while also implicating HIF-1α and VHL in this regulation.

    • Bonnie Huang
    • , James D. Phelan
    •  & Pamela L. Schwartzberg

  • Article
    | Open Access

    Biocontainment is a key to developing safe genetically-engineered microbes (GEMs). Here the authors demonstrate genetically stable CRISPR-based kill switches that control GEMs’ viability in animal hosts, enabling their safe biomedical applications.

    • Austin G. Rottinghaus
    • , Aura Ferreiro
    •  & Tae Seok Moon

  • Article
    | Open Access

    Anti-deaminases can inhibit APOBEC3, a component of cytosine base editors. Here Zhanjun Li and colleagues repurposed anti-deaminase proteins derived from viruses to inhibit base editors for use in efficient regulation of base editors’ activity in gene modification and therapeutic applications.

    • Zhiquan Liu
    • , Siyu Chen
    •  & Zhanjun Li

  • Article
    | Open Access

    The sequence determinants governing CRISPR/Cas9 specificity are not fully understood. Here, the authors devise a high-throughput dual-target synthetic system to explore the sequence features associated with CRISPR/Cas9 off-target effect, reveal a set of sequence-dependent rules, and develop an off-target prediction model and a strategy for Cas9-based allele-specific editing.

    • Rongjie Fu
    • , Wei He
    •  & Han Xu

  • Article
    | Open Access

    In vivo assessment of nuclease off-target activity has primarily been indirect or through ChIP-based detection of double-strand break DNA repair factors, which can be cumbersome. Here, the authors show that GUIDE-tag, enables one-step off-target genome editing analysis in mouse liver and lung.

    • Shun-Qing Liang
    • , Pengpeng Liu
    •  & Wen Xue

  • Article
    | Open Access

    CRISPR-based engineering can be used to bias sex ratios. Here the authors develop a transgenic line of Drosophila melanogaster expressing Cas9 from the Y chromosome and functionally characterize the utility of this strain for both sex selection and gene drive.

    • Stephanie Gamez
    • , Duverney Chaverra-Rodriguez
    •  & Omar S. Akbari

  • Article
    | Open Access

    The diamondback moth is a cosmopolitan pest of significant economic importance. Here the authors analyse globally distributed genomic data to find evidence of climate-associated adaptive variation, and use an ecogenetic index to predict that it will maintain a global pest status under climate change.

    • Yanting Chen
    • , Zhaoxia Liu
    •  & Shijun You

  • Article
    | Open Access

    In areas such as animal research and agriculture a single sex is often required in abundance, leading to wasted resources and ethical considerations. Here the authors develop a CRISPR/Cas9 mediated synthetic lethal system that enables the production of single sex offspring that can be repurposed for use in multiple organisms.

    • Charlotte Douglas
    • , Valdone Maciulyte
    •  & James M. A. Turner

  • Article
    | Open Access

    Engineering biosynthetic assembly lines is a powerful path to new natural products but is challenging with current methods. Here the authors use CRISPR-Cas9 to exchange subdomains within NRPS to alter substrate selectivity.

    • Wei Li Thong
    • , Yingxin Zhang
    •  & Jason Micklefield

  • Article
    | Open Access

    Forward genetic approaches such as CRISPR screens are powerful ways to identify essential genes and those that influence host-pathogen interactions. Here the authors design a bioinformatics portal for sgRNA design and a recombination-mediated cassette system for delivery into mosquito cell lines.

    • Raghuvir Viswanatha
    • , Enzo Mameli
    •  & Norbert Perrimon

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