Improved prime editors enable pathogenic allele correction and cancer modelling in adult mice DOI Creative Commons
Pengpeng Liu, Shun‐Qing Liang, Chunwei Zheng

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: April 9, 2021

Abstract Prime editors (PEs) mediate genome modification without utilizing double-stranded DNA breaks or exogenous donor as a template. PEs facilitate nucleotide substitutions local insertions deletions within the based on template sequence encoded prime editing guide RNA (pegRNA). However, efficacy of in adult mice has not been established. Here we report an NLS-optimized SpCas9-based editor that improves efficiency both fluorescent reporter cells and at endogenous loci cultured cell lines. Using this system, could also seed tumor formation through somatic mouse. Finally, successfully utilize dual adeno-associated virus (AAVs) for delivery split-intein demonstrate system enables correction pathogenic mutation mouse liver. Our findings further establish broad potential technology directed installation modifications vivo, with important implications disease modeling correction.

Language: Английский

Metal and Metalloid Toxicity in Plants: An Overview on Molecular Aspects DOI Creative Commons
Paola Isabel Angulo‐Bejarano, Jonathan Puente-Rivera, Rocío Cruz‐Ortega

et al.

Plants, Journal Year: 2021, Volume and Issue: 10(4), P. 635 - 635

Published: March 27, 2021

Worldwide, the effects of metal and metalloid toxicity are increasing, mainly due to anthropogenic causes. Soil contamination ranks among most important factors, since it affects crop yield, metals/metalloids can enter food chain undergo biomagnification, having concomitant on human health alterations environment. Plants have developed complex mechanisms overcome these biotic abiotic stresses during evolution. Metals metalloids exert several plants generated by elements such as Zn, Cu, Al, Pb, Cd, As, others. The main strategies involve hyperaccumulation, tolerance, exclusion, chelation with organic molecules. Recent studies in omics era increased knowledge plant genome transcriptome plasticity defend against stimuli. aim present review is summarize relevant findings which take up, accumulate, transport, tolerate, respond this metal/metalloid stress. We also address some potential applications biotechnology improve tolerance or increase accumulation.

Language: Английский

Citations

256

mRNA-based cancer therapeutics DOI
Chuang LIU,

Qiangqiang Shi,

Xiangang Huang

et al.

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(8), P. 526 - 543

Published: June 13, 2023

Language: Английский

Citations

226

Current understanding of osteoarthritis pathogenesis and relevant new approaches DOI Creative Commons
Liping Tong, Huan Yu, Xingyun Huang

et al.

Bone Research, Journal Year: 2022, Volume and Issue: 10(1)

Published: Sept. 20, 2022

Abstract Osteoarthritis (OA) is the most common degenerative joint disease that causes painful swelling and permanent damage to joints in body. The molecular mechanisms of OA are currently unknown. a heterogeneous affects entire joint, multiple tissues altered during development. To better understand pathological OA, new approaches, methods, techniques need be used pathogenesis. In this review, we first focus on epigenetic regulation with particular DNA methylation, histone modification, microRNA regulation, followed by summary several key mediators OA-associated pain. We then introduce innovative have been will continue fields pain, such as CRISPR, scRNA sequencing, lineage tracing. Next, discuss timely updates concerning cell death pathology, including pyroptosis, ferroptosis, autophagy, well their individual roles potential targets treating OA. Finally, our review highlights directions role synovial lymphatic system An improved understanding pathogenesis aid development more specific effective therapeutic interventions for

Language: Английский

Citations

224

CRISPRCasTyper: Automated Identification, Annotation, and Classification of CRISPR-Cas Loci DOI
Jakob Russel, Rafael Pinilla‐Redondo, David Mayo-Muñoz

et al.

The CRISPR Journal, Journal Year: 2020, Volume and Issue: 3(6), P. 462 - 469

Published: Dec. 1, 2020

Automated classification of CRISPR-Cas systems has been challenged by their dynamic nature and expanding classification. Here, we developed CRISPRCasTyper, an automated tool with improved capabilities for identifying typing CRISPR arrays cas loci based on the latest nomenclature (44 subtypes/variants). As a novel feature, CRISPRCasTyper uses machine learning approach to subtype sequences repeats, which allows orphan distant arrays. provides graphical output, where CRISPRs operons are visualized as gene maps, thus aiding annotation partial through synteny. was benchmarked against manually curated set 31 subtypes median accuracy 98.6% used explore diversity across >3,000 metagenomes. Altogether, present up-to-date software prediction loci. is available conda web server (cctyper.crispr.dk).

Language: Английский

Citations

223

Improved prime editors enable pathogenic allele correction and cancer modelling in adult mice DOI Creative Commons
Pengpeng Liu, Shun‐Qing Liang, Chunwei Zheng

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: April 9, 2021

Abstract Prime editors (PEs) mediate genome modification without utilizing double-stranded DNA breaks or exogenous donor as a template. PEs facilitate nucleotide substitutions local insertions deletions within the based on template sequence encoded prime editing guide RNA (pegRNA). However, efficacy of in adult mice has not been established. Here we report an NLS-optimized SpCas9-based editor that improves efficiency both fluorescent reporter cells and at endogenous loci cultured cell lines. Using this system, could also seed tumor formation through somatic mouse. Finally, successfully utilize dual adeno-associated virus (AAVs) for delivery split-intein demonstrate system enables correction pathogenic mutation mouse liver. Our findings further establish broad potential technology directed installation modifications vivo, with important implications disease modeling correction.

Language: Английский

Citations

221