Abstract:
:CRISPR/Cas9 technology offers novel approaches for the development of new therapies for many unmet clinical needs, including a significant number of inherited monogenic diseases. However, in vivo correction of disease-causing genes is still inefficient, especially for those diseases without selective advantage for corrected cells. We reasoned that substrate reduction therapies (SRT) targeting non-essential enzymes could provide an attractive alternative. Here we evaluate the therapeutic efficacy of an in vivo CRISPR/Cas9-mediated SRT to treat primary hyperoxaluria type I (PH1), a rare inborn dysfunction in glyoxylate metabolism that results in excessive hepatic oxalate production causing end-stage renal disease. A single systemic administration of an AAV8-CRISPR/Cas9 vector targeting glycolate oxidase, prevents oxalate overproduction and kidney damage, with no signs of toxicity in Agxt1-/- mice. Our results reveal that CRISPR/Cas9-mediated SRT represents a promising therapeutic option for PH1 that can be potentially applied to other metabolic diseases caused by the accumulation of toxic metabolites.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Zabaleta N,Barberia M,Martin-Higueras C,Zapata-Linares N,Betancor I,Rodriguez S,Martinez-Turrillas R,Torella L,Vales A,Olagüe C,Vilas-Zornoza A,Castro-Labrador L,Lara-Astiaso D,Prosper F,Salido E,Gonzalez-Aseguinolaza G,Rdoi
10.1038/s41467-018-07827-1subject
Has Abstractpub_date
2018-12-21 00:00:00pages
5454issue
1issn
2041-1723pii
10.1038/s41467-018-07827-1journal_volume
9pub_type
杂志文章abstract::Understanding human mobility is crucial for applications such as forecasting epidemic spreading, planning transport infrastructure and urbanism in general. While, traditionally, mobility information has been collected via surveys, the pervasive adoption of mobile technologies has brought a wealth of (real time) data. ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11841-2
更新日期:2019-08-29 00:00:00
abstract::Understanding the details of domain wall (DW) motion along magnetic racetracks has drawn considerable interest in the past few years for their applications in non-volatile memory devices. The propagation of the DW is dictated by the interplay between its driving force, either field or current, and the complex energy l...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms1024
更新日期:2010-06-15 00:00:00
abstract::Electric fields at interfaces exhibit useful phenomena, such as switching functions in transistors, through electron accumulations and/or electric dipole inductions. We find one potentially unique situation in a metal-dielectric interface in which the electric field is atomically inhomogeneous because of the strong el...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms15848
更新日期:2017-06-23 00:00:00
abstract::CrAss-like phages are double-stranded DNA viruses that are prevalent in human gut microbiomes. Here, we analyze gut metagenomic data from mother-infant pairs and patients undergoing fecal microbiota transplantation to evaluate the patterns of acquisition, transmission and strain diversity of crAss-like phages. We find...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-14103-3
更新日期:2020-01-15 00:00:00
abstract::Replication and transcription of genomic DNA requires partial disassembly of nucleosomes to allow progression of polymerases. This presents both an opportunity to remodel the underlying chromatin and a danger of losing epigenetic information. Centromeric transcription is required for stable incorporation of the centro...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-16695-7
更新日期:2020-06-10 00:00:00
abstract::Lysosomes are the major degradative compartments within cells, harbouring a wide variety of hydrolytic enzymes within their lumen. Release of lysosomal hydrolases from lysosomes into the cell cytoplasm results in cell death. Here we report that damaged lysosomes undergo autophagic turnover. Using a light-induced lysos...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3111
更新日期:2013-01-01 00:00:00
abstract::The design and assembly of artificial protocell consortia displaying dynamical behaviours and systems-based properties are emerging challenges in bottom-up synthetic biology. Cellular processes such as morphogenesis and differentiation rely in part on reaction-diffusion gradients, and the ability to mimic rudimentary ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11316-4
更新日期:2019-07-25 00:00:00
abstract::HIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide ("Man9-V3") for structural studies of an HIV Env third variable loop (V3)-glycan directed, broadly neutralizing antibody (bnAb) lineage ("DH270"), to visualize the epitope...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03565-6
更新日期:2018-03-16 00:00:00
abstract::Monolayer transition metal dichalcogenides integrated in optical microcavities host exciton-polaritons as a hallmark of the strong light-matter coupling regime. Analogous concepts for hybrid light-matter systems employing spatially indirect excitons with a permanent electric dipole moment in heterobilayer crystals pro...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11620-z
更新日期:2019-08-16 00:00:00
abstract::Familial hemiplegic migraine is an episodic neurological disorder characterized by transient sensory and motor symptoms and signs. Mutations of the ion pump α2-Na/K ATPase cause familial hemiplegic migraine, but the mechanisms by which α2-Na/K ATPase mutations lead to the migraine phenotype remain incompletely underst...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-19915-2
更新日期:2020-12-02 00:00:00
abstract::Manipulation of proteins by chemical modification is a powerful way to decipher their function. However, most ribosome-dependent and semi-synthetic methods have limitations in the number and type of modifications that can be introduced, especially in live cells. Here, we present an approach to incorporate single or mu...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-16208-6
更新日期:2020-05-08 00:00:00
abstract::The mammary gland undergoes cycles of growth and regeneration throughout reproductive life, a process that requires mammary stem cells (MaSCs). Whilst recent genetic fate-mapping studies using lineage-specific promoters have provided valuable insights into the mammary epithelial hierarchy, the true differentiation pot...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms13053
更新日期:2016-10-25 00:00:00
abstract::During epithelial morphogenesis, cell contacts (junctions) are constantly remodeled by mechanical forces that work against adhesive forces. E-cadherin complexes play a pivotal role in this process by providing persistent cell adhesion and by transmitting mechanical tension. In this context, it is unclear how mechanica...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07448-8
更新日期:2018-11-27 00:00:00
abstract::Zika virus is a mosquito-borne flavivirus closely related to dengue virus that can cause severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Specific treatments and vaccines for Zika virus are not currently available. Here, we isolate and characterize four monoclonal ant...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07008-0
更新日期:2018-11-01 00:00:00
abstract::Controlling the properties of quantum dots at the atomic scale, such as dangling bonds, is a general motivation as they allow studying various nanoscale processes including atomic switches, charge storage, or low binding energy state interactions. Adjusting the coupling of individual silicon dangling bonds to form a 2...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-02377-4
更新日期:2017-12-20 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature communications
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41467-020-18712-1
更新日期:2020-09-16 00:00:00
abstract::Gold recovery using environmentally benign chemistry is imperative from an environmental perspective. Here we report the spontaneous assembly of a one-dimensional supramolecular complex with an extended {[K(OH₂)₆][AuBr₄](α-cyclodextrin)₂}n chain superstructure formed during the rapid co-precipitation of α-cyclodextrin...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms2891
更新日期:2013-01-01 00:00:00
abstract::Expression of the matricellular protein CCN1 (CYR61) is associated with inflammation and is required for successful wound repair. Here, we show that CCN1 binds bacterial pathogen-associated molecular patterns including peptidoglycans of Gram-positive bacteria and lipopolysaccharides of Gram-negative bacteria. CCN1 ops...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-15075-5
更新日期:2020-03-06 00:00:00
abstract::Current knowledge on chromosomal mosaicism in human cell cultures is mostly based on cytogenetic banding methods. The recent development of high-resolution full-genome analysis methods applicable to single cells is providing new insights into genetic and cellular diversity. Here we study the genetic content of 92 indi...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms5227
更新日期:2014-06-27 00:00:00
abstract::Self-sustaining oscillations are essential for diverse physiological functions such as the cell cycle, insulin secretion and circadian rhythms. Synthetic oscillators using biochemical feedback circuits have been generated in cell culture. These synthetic systems provide important insight into design principles for bio...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9587
更新日期:2015-11-30 00:00:00
abstract::The role of microglia in spinal cord injury (SCI) remains poorly understood and is often confused with the response of macrophages. Here, we use specific transgenic mouse lines and depleting agents to understand the response of microglia after SCI. We find that microglia are highly dynamic and proliferate extensively ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-08446-0
更新日期:2019-01-31 00:00:00
abstract::The photon-like behavior of electrons in graphene causes unusual confinement properties that depend strongly on the geometry and strength of the surrounding potential. We report bottom-up synthesis of atomically-precise one-dimensional (1D) arrays of point charges on graphene that allow exploration of a new type of su...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-08371-2
更新日期:2019-01-29 00:00:00
abstract::Real-time imaging of moving organs and tissues at microscopic resolutions represents a major challenge in studying the complex biology of live animals. Here we present a technique based on a novel stabilizer setup combined with a gating acquisition algorithm for the imaging of a beating murine heart at the single-cell...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms2060
更新日期:2012-01-01 00:00:00
abstract::Chemical clocks are often used as exciting classroom experiments, where an induction time is followed by rapidly changing colours that expose oscillating concentration patterns. This type of reaction belongs to a class of nonlinear chemical kinetics also linked to chaos, wave propagation and Turing patterns. Despite i...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms11832
更新日期:2016-06-10 00:00:00
abstract::BRCA2 is essential for maintaining genomic integrity. BRCA2-deficient primary cells are either not viable or exhibit severe proliferation defects. Yet, BRCA2 deficiency contributes to tumorigenesis. It is believed that mutations in genes such as TRP53 allow BRCA2 heterozygous cells to overcome growth arrest when they ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03020-6
更新日期:2018-02-07 00:00:00
abstract::The leaf economics spectrum (LES) describes consistent correlations among a variety of leaf traits that reflect a gradient from conservative to acquisitive plant strategies. So far, whether the LES holds in wetland plants at a global scale has been unclear. Using data on 365 wetland species from 151 studies, we find t...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-18354-3
更新日期:2020-09-09 00:00:00
abstract::Dynamics are fundamental to the functions of biomolecules and can occur on a wide range of time and length scales. Here we develop and apply high-speed AFM height spectroscopy (HS-AFM-HS), a technique whereby we monitor the sensing of a HS-AFM tip at a fixed position to directly detect the motions of unlabeled molecul...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07512-3
更新日期:2018-11-26 00:00:00
abstract::Nonbiaryl N-C atropisomer is an important structural scaffold, which is present in natural products, medicines and chiral ligands. However the direct enantioselective C-H amination to access optically pure N-C atropisomer is still difficult and rare. Here we report a π-π interaction and dual H-bond concerted control s...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-10858-x
更新日期:2019-07-11 00:00:00
abstract::TorsinA is an ER-resident AAA + ATPase, whose deletion of glutamate E303 results in the genetic neuromuscular disease primary dystonia. TorsinA is an unusual AAA + ATPase that needs an external activator. Also, it likely does not thread a peptide substrate through a narrow central channel, in contrast to its closest s...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11194-w
更新日期:2019-07-22 00:00:00
abstract::Identification of the optimal quantum metrological protocols in realistic many particle quantum models is in general a challenge that cannot be efficiently addressed by the state-of-the-art numerical and analytical methods. Here we provide a comprehensive framework exploiting matrix product operators (MPO) type tensor...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-13735-9
更新日期:2020-01-14 00:00:00