Publications by authors named "Guoling Li"

Duplication of methyl-CpG-binding protein 2 (MECP2) gene causes MECP2 duplication syndrome (MDS). To normalize the duplicated MECP2 in MDS, we developed a high-fidelity Cas13Y (hfCas13Y) system capable of targeting the MECP2 (hfCas13Y-gMECP2) messenger RNA for degradation and reducing protein levels in the brain of humanized MECP2 transgenic mice. Moreover, the intracerebroventricular adeno-associated virus (AAV) delivery of hfCas13Y-gMECP2 in newborn or adult MDS mice restored dysregulated gene expression and improved behavior deficits.

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IscBs, as hypercompact ancestry proteins of Cas9 nuclease, are suitable for in vivo gene editing via single adeno-associated virus (AAV) delivery. Due to the low activity of natural IscBs in eukaryotic cells, recent studies have been focusing on improving OgeuIscB's gene editing efficiency via protein engineering. However, in vivo gene editing efficacy of IscBs for disease correction remained to be demonstrated.

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Article Synopsis
  • Electrolytic seawater presents a sustainable and cost-effective method for hydrogen production, with transition metal phosphides serving as effective catalysts for water electrolysis.
  • The study successfully synthesizes coated NiFeP nanocrystals with a unique porous rugby shape, utilizing Ar-H plasma to create these structures at low temperatures.
  • The resulting NiFeP catalyst demonstrates impressive performance in alkaline conditions, showing excellent catalytic activity, corrosion resistance, and stability for over 100 hours, while theoretical calculations explain improved reaction efficiency through specific modifications.
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  • * Current TadA variants are limited by their preference for specific DNA motifs and dual activity on both cytosine and adenosine, which restricts their use.
  • * Researchers developed a new cytosine base editor (aTdCBE) that overcomes these limitations and successfully tested it in a humanized mouse model for Duchenne muscular dystrophy, restoring dystrophin expression.
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As the evolutionary ancestor of Cas9 nuclease, IscB proteins serve as compact RNA-guided DNA endonucleases and nickases, making them strong candidates for base editing. Nevertheless, the narrow targeting scope limits the application of IscB systems; thus, it is necessary to find more IscBs that recognize different target-adjacent motifs (TAMs). Here, we identified 10 of 19 uncharacterized IscB proteins from uncultured microbes with activity in mammalian cells.

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Duchenne muscular dystrophy (DMD) affecting 1 in 3500-5000 live male newborns is the frequently fatal genetic disease resulted from various mutations in DMD gene encoding dystrophin protein. About 70% of DMD-causing mutations are exon deletion leading to frameshift of open reading frame and dystrophin deficiency. To facilitate translating human DMD-targeting CRISPR therapeutics into patients, we herein establish a genetically humanized mouse model of DMD by replacing exon 50 and 51 of mouse Dmd gene with human exon 50 sequence.

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DNA base editors enable direct editing of adenine (A), cytosine (C), or guanine (G), but there is no base editor for direct thymine (T) editing currently. Here we develop two deaminase-free glycosylase-based base editors for direct T editing (gTBE) and C editing (gCBE) by fusing Cas9 nickase (nCas9) with engineered human uracil DNA glycosylase (UNG) variants. By several rounds of structure-informed rational mutagenesis on UNG in cultured human cells, we obtain gTBE and gCBE with high activity of T-to-S (i.

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  • Sn and C nanocomposites are promising anode materials for lithium-ion batteries, but their synthesis remains a challenge for practical use.
  • A new one-step method is introduced that uses mechanical milling to create very small Sn nanocrystals (less than 5 nm) on carbon black, improving the synthesis process.
  • The resulting Sn@C electrode shows impressive battery performance with high capacity, excellent rate ability, and stability over many charging cycles.
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The electrochemical splitting of seawater is promising but also challenging for sustainable hydrogen gas production. Herein, ZIF-67 nanosheets are grown on nickel foam and then etched by Ni in situ to obtain a hierarchical hollow nanosheets structure, which demonstrates outstanding OER performance in alkaline seawater (355 mV at 100 mA cm). Diven by a silicon solar panel, an overall electrolysis energy efficiency of 62% is achieved at a high current of 100 mA cm in seawater electrolytes.

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Duchenne muscular dystrophy (DMD) is the most prevalent herediatry disease in men, characterized by dystrophin deficiency, progressive muscle wasting, cardiac insufficiency, and premature mortality, with no effective therapeutic options. Here, we investigated whether adenine base editing can correct pathological nonsense point mutations leading to premature stop codons in the dystrophin gene. We identified 27 causative nonsense mutations in our DMD patient cohort.

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Design of flexible porous materials where the diffusion of guest molecules is regulated by the dynamics of contracted pore aperture is challenging. Here, a flexible porous self-assembly consisting of 1D channels with dynamic bottleneck gates is reported. The dynamic pendant naphthimidazolylmethyl moieties at the channel necks provide kinetic gate function, that enables unusual adsorption for light hydrocarbons.

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Transposon-associated ribonucleoprotein TnpB is known to be the ancestry endonuclease of diverse Cas12 effector proteins from type-V CRISPR system. Given its small size (408 aa), it is of interest to examine whether engineered TnpB could be used for efficient mammalian genome editing. Here, we showed that the gene editing activity of native TnpB from Deinococcus radiodurans (ISDra2 TnpB) in mouse embryos was already higher than previously identified small-sized Cas12f1.

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Background: Gene knock-in (KI) in animal cells via homology-directed repair (HDR) is an inefficient process, requiring a laborious work for screening from few modified cells. HDR tends to occur in the S and G2/M phases of cell cycle; therefore, strategies that enhance the proportion of cells in these specific phases could improve HDR efficiency.

Results: We used various types of cell cycle inhibitors to synchronize the cell cycle in S and G2/M phases in order to investigate their effect on regulating CRISPR/Cas9-mediated HDR.

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Graphene cladded cobalt phosphide nanoparticles with a sandwich structure are synthesized using Ar-H2-P plasma. phosphorization and graphene reduction are achieved at the same time. Benefitting from the sandwich structure and heterointerface between CoP and RGO, the electrode delivered a high reversible capacity and durable lifespan for both lithium and sodium storage.

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Ester hydrates, as the intermediates of the esterification between acid and alcohol, are very short-lived and challenging to be trapped. Therefore, the crystal structures of ester hydrates have rarely been characterized. Herein, we present that the mono-deprotonated ester hydrates [CHOSO(OH)], serving as the template for the self-assembly of a π-stacked boat-shaped macrocycle (CHOSO(OH))(CHOSO)@{[ClLCo]}·Cl·13CHOH·9HO () (L = tris(2-benzimidazolylmethyl) amine), can be trapped in the host by multiple NH···O hydrogen bonds.

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Single-crystal-to-single-crystal metalation of organic ligands represents a novel method to prepare metal-organic complexes, but remains challenging. Herein, a hierarchical self-assembly {(HL)·([N(CH)])·(ClO)·(HO)} () (L = tris(2-benzimidazolylmethyl) amine) consisting of -stacked cubes which are assembled from eight partially protonated L ligands is obtained. By soaking the crystals of compound in the aqueous solution of Co(SCN), the ligands coordinate with Co ions stoichiometrically and ClO exchange with SCN via single-crystal-to-single-crystal transformation, leading to {([CoSCNL])·([NCH])·(SCN)·(HO)} ().

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Current DNA base editors contain nuclease and DNA deaminase that enables deamination of cytosine (C) or adenine (A), but no method for guanine (G) or thymine (T) editing is available at present. Here we developed a deaminase-free glycosylase-based guanine base editor (gGBE) with G editing ability, by fusing Cas9 nickase with engineered N-methylpurine DNA glycosylase protein (MPG). By several rounds of MPG mutagenesis via unbiased and rational screening using an intron-split EGFP reporter, we demonstrated that gGBE with engineered MPG could increase G editing efficiency by more than 1500 fold.

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A targeted defect-induced strategy of metal sites in a porous framework is an efficient avenue to improve the performance of a catalyst. However, achieving such an activation without destroying the ordered framework is a major challenge. Herein, a dielectric barrier discharge plasma can etch the Fe(CN) group of the NiFe Prussian blue analogue framework in situ through reactive oxygen species generated in the air.

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As a miniature RNA-guided endonuclease, IscB is presumed to be the ancestor of Cas9 and to share similar functions. IscB is less than half the size of Cas9 and thus more suitable for in vivo delivery. However, the poor editing efficiency of IscB in eukaryotic cells limits its in vivo applications.

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Article Synopsis
  • Researchers developed a new RNA base editor called compact and efficient RNA base editor (ceRBE) that replaces the larger dCas13 protein, improving its in vivo application capabilities.
  • The ceRBE efficiently edits adenine-to-inosine (A-to-I) and cytidine-to-uridine (C-to-U) while minimizing off-target effects in HEK293T cells.
  • In a humanized mouse model for Duchenne muscular dystrophy, ceRBE successfully repaired a mutation and restored gene expression, indicating its potential for treating genetic diseases.
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The type V-F CRISPR-Cas12f system is a strong candidate for therapeutic applications due to the compact size of the Cas12f proteins. In this work, we identify six uncharacterized Cas12f1 proteins with nuclease activity in mammalian cells from assembled bacterial genomes. Among them, OsCas12f1 (433 aa) from Oscillibacter sp.

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Approximately 10% of monogenic diseases are caused by nonsense point mutations that generate premature termination codons (PTCs), resulting in a truncated protein and nonsense-mediated decay of the mutant mRNAs. Here, we demonstrate a mini-dCas13X-mediated RNA adenine base editing (mxABE) strategy to treat nonsense mutation-related monogenic diseases via A-to-G editing in a genetically humanized mouse model of Duchenne muscular dystrophy (DMD). Initially, we identified a nonsense point mutation (c.

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