Abstract:
:CRISPR-Cas systems have revolutionized genome editing across a broad range of biotechnological endeavors. Many CRISPR-Cas nucleases have been identified and engineered for improved capabilities. Given the modular structure of such enzymes, we hypothesized that engineering chimeric sequences would generate non-natural variants that span the kinetic parameter landscape, and thus provide for the rapid selection of nucleases fit for a particular editing system. Here, we design a chimeric Cas12a-type library with approximately 560 synthetic chimeras, and select several functional variants. We demonstrate that certain nuclease domains can be recombined across distantly related nuclease templates to produce variants that function in bacteria, yeast, and human cell lines. We further characterize selected chimeric nucleases and find that they have different protospacer adjacent motif (PAM) preferences and the M44 chimera has higher specificity relative to wild-type (WT) sequences. This demonstration opens up the possibility of generating nuclease sequences with implications across biotechnology.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Liu RM,Liang LL,Freed E,Chang H,Oh E,Liu ZY,Garst A,Eckert CA,Gill RTdoi
10.1038/s41467-019-13500-ysubject
Has Abstractpub_date
2019-12-04 00:00:00pages
5524issue
1issn
2041-1723pii
10.1038/s41467-019-13500-yjournal_volume
10pub_type
杂志文章abstract::The development of native-like HIV-1 envelope (Env) trimer antigens has enabled the induction of neutralizing antibody (NAb) responses against neutralization-resistant HIV-1 strains in animal models. However, NAb responses are relatively weak and narrow in specificity. Displaying antigens in a multivalent fashion on n...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12080-1
更新日期:2019-09-19 00:00:00
abstract::Vesicular photothermal therapy agents (PTAs) are highly desirable in photothermal therapy (PTT) for their excellent light-harvesting ability and versatile hollow compartments. However, up to now, the reported vesicular PTAs are generally self-assembled from small molecules like liposomes, and polymer vesicles have sel...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-15427-1
更新日期:2020-04-07 00:00:00
abstract::Accurate prediction of an individual's phenotype from their DNA sequence is one of the great promises of genomics and precision medicine. We extend a powerful individual-level data Bayesian multiple regression model (BayesR) to one that utilises summary statistics from genome-wide association studies (GWAS), SBayesR. ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12653-0
更新日期:2019-11-08 00:00:00
abstract::Transition-metal dissolution from cathode materials, manganese in particular, has been held responsible for severe capacity fading in lithium-ion batteries, with the deposition of the transition-metal cations on anode surface, in elemental form or as chelated-complexes, as the main contributor for such degradations. I...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11439-8
更新日期:2019-07-31 00:00:00
abstract::Recent studies suggest that gut microbiomes of urban-industrialized societies are different from those of traditional peoples. Here we examine the relationship between lifeways and gut microbiota through taxonomic and functional potential characterization of faecal samples from hunter-gatherer and traditional agricult...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms7505
更新日期:2015-03-25 00:00:00
abstract::Inorganic polyphosphate is known to be present in the mammalian brain at micromolar concentrations. Here we show that polyphosphate may act as a gliotransmitter, mediating communication between astrocytes. It is released by astrocytes in a calcium-dependent manner and signals to neighbouring astrocytes through P2Y(1) ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms2364
更新日期:2013-01-01 00:00:00
abstract::Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleo...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9754
更新日期:2015-10-30 00:00:00
abstract::Emerging evidence indicates that osteoclasts direct osteoblastic bone formation. MicroRNAs (miRNAs) have a crucial role in regulating osteoclast and osteoblast function. However, whether miRNAs mediate osteoclast-directed osteoblastic bone formation is mostly unknown. Here, we show that increased osteoclastic miR-214-...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms10872
更新日期:2016-03-07 00:00:00
abstract::The ribosome stalls on translation of polyproline sequences due to inefficient peptide bond formation between consecutive prolines. The translation factor EF-P is able to alleviate this stalling by accelerating Pro-Pro formation. However, the mechanism by which EF-P recognizes the stalled complexes and accelerates pep...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11657
更新日期:2016-05-24 00:00:00
abstract::Achieving control over the directionality of active colloids is essential for their use in practical applications such as cargo carriers in microfluidic devices. So far, guidance of spherical Janus colloids was mainly realized using specially engineered magnetic multilayer coatings combined with external magnetic fiel...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms10598
更新日期:2016-02-09 00:00:00
abstract::Accumulating evidence suggests that transcriptional regulation is required for maintenance of long-term memories (LTMs). Here we characterize global transcriptional and epigenetic changes that occur during LTM storage in the Drosophila mushroom bodies (MBs), structures important for memory. Although LTM formation requ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms13471
更新日期:2016-11-14 00:00:00
abstract::ASXL1 mutations occur frequently in myeloid neoplasms and are associated with poor prognosis. However, the mechanisms by which mutant ASXL1 induces leukaemogenesis remain unclear. In this study, we report mutually reinforcing effects between a C-terminally truncated form of mutant ASXL1 (ASXL1-MT) and BAP1 in promotin...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-05085-9
更新日期:2018-07-16 00:00:00
abstract::The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favoured development of epigenetic drugs. In this study, we design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity....
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms15424
更新日期:2017-05-26 00:00:00
abstract::Epilepsy is a common brain disorder throughout history. Epilepsy-related ligand-receptor complex, LGI1-ADAM22, regulates synaptic transmission and has emerged as a determinant of brain excitability, as their mutations and acquired LGI1 autoantibodies cause epileptic disorders in human. Here, we report the crystal stru...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03947-w
更新日期:2018-04-18 00:00:00
abstract::Hedgehog (Hh) signalling regulates embryonic development and adult tissue homoeostasis. Mutations of its pathway components including Suppressor of Fused (Sufu) and Gli/Ci predispose to cancers and congenital anomalies. The Sufu-Gli protein complex occupies a central position in the vertebrate Hh signalling pathway, e...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3608
更新日期:2013-01-01 00:00:00
abstract::Hydrosilylation of allenes is the addition of a hydrogen atom and a silyl group to a carbon-carbon double bond of an allene molecule and represents a straightforward and atom-economical approach to prepare synthetically versatile allylsilanes and vinylsilanes. However, this reaction generally produces six possible iso...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-02382-7
更新日期:2017-12-22 00:00:00
abstract::Oxygen vacancies in proximity to surfaces and heterointerfaces in oxide thin film heterostructures have major effects on properties, resulting, for example, in emergent conduction behaviour, large changes in metal-insulator transition temperatures or enhanced catalytic activity. Here we report the discovery of a means...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11892
更新日期:2016-06-10 00:00:00
abstract::Cell-to-cell variability (noise) is an important feature of gene expression that impacts cell fitness and development. The regulatory mechanism of this variability is not fully understood. Here we investigate the effect on gene expression noise in divergent gene pairs (DGPs). We generated reporters driven by divergent...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11099
更新日期:2016-03-24 00:00:00
abstract::Chirality is an intriguing property of certain molecules, materials or artificial nanostructures, which allows them to interact with the spin angular momentum of the impinging light field. Due to their chiral geometry, they can distinguish between left- and right-hand circular polarization states or convert them into ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms13117
更新日期:2016-10-13 00:00:00
abstract::Mutators represent a successful strategy in rapidly adapting asexual populations, but theory predicts their eventual extinction due to their unsustainably large deleterious load. While antimutator invasions have been documented experimentally, important discrepancies among studies remain currently unexplained. Here we...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11217-6
更新日期:2019-07-15 00:00:00
abstract::Single-nucleotide substitutions are a defining characteristic of cancer genomes. Many single-nucleotide substitutions in cancer genomes arise because of errors in DNA replication, which is spatio-temporally stratified. Here we propose that DNA replication patterns help shape the mutational landscapes of normal and can...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms2502
更新日期:2013-01-01 00:00:00
abstract::The continued development of novel drugs, proteins, and advanced materials strongly rely on our ability to self-assemble molecules in solids with the most suitable structure (polymorph) in order to exhibit desired functionalities. The search for new polymorphs remains a scientific challenge, that is at the core of cry...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11555
更新日期:2016-05-10 00:00:00
abstract::The stem cell pluripotency factor Oct4 serves a critical protective role during atherosclerotic plaque development by promoting smooth muscle cell (SMC) investment. Here, we show using Myh11-CreERT2 lineage-tracing with inducible SMC and pericyte (SMC-P) knockout of Oct4 that Oct4 regulates perivascular cell migration...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-08811-z
更新日期:2019-02-27 00:00:00
abstract::HOXA9 and MEIS1 have essential oncogenic roles in mixed lineage leukaemia (MLL)-rearranged leukaemia. Here we show that they are direct targets of miRNA-196b, a microRNA (miRNA) located adjacent to and co-expressed with HOXA9, in MLL-rearranged leukaemic cells. Forced expression of miR-196b significantly delays MLL-fu...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms1681
更新日期:2012-02-21 00:00:00
abstract::The hallmark of Salmonella Typhimurium infection is an acute intestinal inflammatory response, which is mediated through the action of secreted bacterial effector proteins. The pro-inflammatory Salmonella effector SopA is a HECT-like E3 ligase, which was previously proposed to activate host RING ligases TRIM56 and TRI...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms14004
更新日期:2017-01-13 00:00:00
abstract::Adeno-associated virus (AAV) capsid engineering is an emerging approach to advance gene therapy. However, a systematic analysis on how each capsid amino acid contributes to multiple functions remains challenging. Here we show proof-of-principle and successful application of a novel approach, termed AAV Barcode-Seq, th...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms4075
更新日期:2014-01-01 00:00:00
abstract::Spectral domain optical coherence tomography (OCT) is a widely employed, minimally invasive bio-medical imaging technique, which requires a broadband light source, typically implemented by super-luminescent diodes. Recent advances in soliton based photonic integrated frequency combs (soliton microcombs) have enabled t...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-20404-9
更新日期:2021-01-18 00:00:00
abstract::Many regulatory and signaling proteins have multiple modification sites. In bacterial chemotaxis, each chemoreceptor has multiple methylation sites that are responsible for adaptation. However, whether the ordering of the multisite methylation process affects adaptation remains unclear. Furthermore, the benefit of hav...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-16644-4
更新日期:2020-06-08 00:00:00
abstract::Human Ebp1 is a member of the proliferation-associated 2G4 (PA2G4) family and plays an important role in cancer regulation. Ebp1 shares the methionine aminopeptidase (MetAP) fold and binds to mature 80S ribosomes for translational control. Here, we present a cryo-EM single particle analysis reconstruction of Ebp1 boun...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-14603-7
更新日期:2020-02-07 00:00:00
abstract::Recent expansion of croplands in the United States has caused widespread conversion of grasslands and other ecosystems with largely unknown consequences for agricultural production and the environment. Here we assess annual land use change 2008-16 and its impacts on crop yields and wildlife habitat. We find that cropl...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-18045-z
更新日期:2020-09-09 00:00:00