A5101823222- CRISPR and Genetic Engineering
- RNA regulation and disease
- Retinal Development and Disorders
- Advanced biosensing and bioanalysis techniques
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Pluripotent Stem Cells Research
- Genetics, Aging, and Longevity in Model Organisms
- RNA Interference and Gene Delivery
- Prenatal Screening and Diagnostics
- Advanced Proteomics Techniques and Applications
- Genetic Syndromes and Imprinting
- Congenital heart defects research
- Nuclear Receptors and Signaling
- Antibiotic Use and Resistance
- Plant Virus Research Studies
- Bacterial Identification and Susceptibility Testing
- Virus-based gene therapy research
- Neurogenetic and Muscular Disorders Research
- Biological Research and Disease Studies
- Skin Protection and Aging
- Cytomegalovirus and herpesvirus research
- RNA and protein synthesis mechanisms
- Thermoregulation and physiological responses
- Cancer-related gene regulation
Jinan University
2025
Center for Excellence in Brain Science and Intelligence Technology
2017-2024
Shanghai Institutes for Biological Sciences
2017-2024
University of Chinese Academy of Sciences
2017-2024
Chinese Academy of Sciences
2017-2023
University of Surrey
2020
Instituto de Ciencias Agrarias
2020
The First Affiliated Hospital, Sun Yat-sen University
2015
Zhongshan Hospital
2015
Fudan University
2015
The CRISPR/Cas9 system is an efficient gene-editing method, but the majority of gene-edited animals showed mosaicism, with editing occurring only in a portion cells. Here we show that single gene or multiple genes can be completely knocked out mouse and monkey embryos by zygotic injection Cas9 mRNA adjacent single-guide RNAs (spaced 10-200 bp apart) target key exon each gene. Phenotypic analysis F0 mice following targeted deletion eight on Y chromosome individually demonstrated robustness...
Abstract DNA base editors, typically comprising editing enzymes fused to the N-terminus of nCas9, display off-target effects on and/or RNA, which have remained an obstacle their clinical applications. Off-target edits are countered via rationally designed point mutations, but approach is tedious and not always effective. Here, we report that both A > G C T editors can be dramatically reduced without compromising on-target simply by inserting into middle nCas9 at tolerant sites identified...
RNA-targeting CRISPR system Cas13 offers an efficient approach for manipulating RNA transcripts in vitro. In this perspective, we provide a proof-of-concept demonstration that Cas13-mediated Vegfa knockdown vivo could prevent the development of laser-induced CNV mouse model Age-related macular degeneration.
Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by loss of function mutations in maternally expressed UBE3A. No gene-specific treatment available for patients so far. Although intact and transcriptionally active, paternally inherited UBE3A silenced elongation antisense long noncoding RNA UBE3A-ATS neurons. Here, we demonstrated that targeting paternal Ube3a-ATS with high-fidelity CRISPR-Cas13 (hfCas13x.1) system could restore Ube3a expression to similar levels as maternal...
ABSTRACT In vivo genetic mutation has become a powerful tool for dissecting gene function; however, multi-gene interaction and the compensatory mechanisms involved can make findings from single mutations, at best difficult to interpret, and, worst, misleading. Hence, it is necessary establish an efficient way disrupt multiple genes simultaneously. CRISPR/Cas9-mediated base editing disrupts function by converting protein-coding sequence into stop codon; this referred as CRISPR-stop. Its...
The coactivator-associated arginine methyltransferase CARM1 catalyzes the methylation of histone H3 17/26 (H3R17/26me) and non-histone proteins at residues to regulate gene transactivation through profiling or Carm1 overexpression assays. However, direct relationship between H3R17/26me its causal role in mouse embryo development remains largely unclear. Here, we use rAPOBEC1-XTEN-Cas9n-UGI (BE3) efficiently introduce a point mutation (R17H) multiple Hist1/2H3 loci premature-stop codon into...
We here report a genome-editing strategy to correct spinal muscular atrophy (SMA). Rather than directly targeting the pathogenic exonic mutations, our employed Cas9 and guide-sgRNA for targeted disruption of intronic splicing-regulatory elements. disrupted splicing silencers (ISSs, including ISS-N1 ISS + 100) survival motor neuron (SMN) 2, key modifier gene SMA, enhance exon 7 inclusion full-length SMN expression in SMA iPSCs. Survival splicing-corrected iPSC-derived neurons was rescued with...
The molecular mechanism associated with mammalian meiosis has yet to be fully explored, and one of the main reasons for this lack exploration is that some meiosis-essential genes are still unknown. profiling gene expression during spermatogenesis been performed in previous studies, few studies have aimed find new functional genes. Since there a huge gap between number able quantified can characterized by phenotype screening assay, an efficient method rank according phenotypic relevance great...
Base editing installs a precise nucleotide change in specific gene loci without causing double-strand break. Its efficiency human embryos is generally low, limiting its utility functional genetic studies. Here, we report that injecting base editors into cleaving two-cell and four-cell results much higher (up to 13-fold) homozygotic substitution as opposed MII oocytes or zygotes. Furthermore, proof-of-principle study, point mutation can be efficiently corrected by our method. Our study...
The safety of CRISPR-based gene editing methods is the utmost priority in clinical applications. Previous studies have reported that Cas9 cleavage induced frequent aneuploidy primary human T cells, but whether cleavage-mediated base editors would generate off-target structure variations remains unknown. Here, we investigate potential structural associated with CRISPR/Cas9, ABE, and CBE mouse embryos cells by whole-genome sequencing single-cell RNA-seq analyses.
Base editors hold promise for correcting pathogenic mutations, while substantial single nucleotide variations (SNVs) on both DNA and RNA were generated by cytosine base (CBEs). Here we examined possibilities to reduce off-target effects engineering deaminases. By screening 24 CBEs harboring various rAPOBEC1 (BE3) or human APOBEC3A (BE3-hA3A) mutations the ssDNA binding domain, found 8 CBE could maintain high on-target editing efficiency. Using Genome-wide Off-target analysis Two-cell embryo...
Abstract DNA base editors, typically comprising editing enzymes fused to the N-terminus of nCas9, display off-target effects on and/or RNA, which have remained a obstacle their clinical applications. Off-target edits are countered via rationally designed point mutations, but approach is tedious and not always effective. Here, we report that both A>G C>T editors can be dramatically reduced without compromising on-target simply by inserting enzyme into middle nCas9 at tolerant sites...
Abstract Williams syndrome is a developmental disorder caused by microdeletion entailing loss of single copy 25-27 genes on chromosome 7q11.23. Patients with suffer from cardiovascular and neuropsychological symptoms. So far, the structural abnormalities system in have been attributed to elastin ( ELN ) gene. In contrast, consequences syndrome, including motor deficits, hypersociability cognitive impairments, mainly altered expression transcription factors like LIMK1, GTF2I GTF2IRD1, while...