A5023979875- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- RNA modifications and cancer
- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Pancreatic function and diabetes
- Liver Disease Diagnosis and Treatment
- Neurogenetic and Muscular Disorders Research
- Cystic Fibrosis Research Advances
- RNA and protein synthesis mechanisms
- Neonatal Respiratory Health Research
- Prostate Cancer Treatment and Research
- Epigenetics and DNA Methylation
- Endoplasmic Reticulum Stress and Disease
- Kruppel-like factors research
- Diabetes and associated disorders
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Advanced Thermodynamic Systems and Engines
- DNA and Nucleic Acid Chemistry
- Photochromic and Fluorescence Chemistry
- Advanced biosensing and bioanalysis techniques
- Muscle Physiology and Disorders
- Mitochondrial Function and Pathology
- Refrigeration and Air Conditioning Technologies
- Liver Diseases and Immunity
Ionis Pharmaceuticals (United States)
2016-2025
Henan University of Technology
2024
Shanghai Ocean University
2023-2024
Qinghai Institute for Endemic Diease Prevention and Control
2022-2023
Xinxiang Medical University
2023
Xuzhou Central Hospital
2023
Sanford Burnham Prebys Medical Discovery Institute
2021
Affiliated Hospital of Chengde Medical College
2013
University of North Carolina at Chapel Hill
2002
Abstract Triantennary N-acetyl galactosamine (GalNAc, GN3), a high-affinity ligand for the hepatocyte-specific asialoglycoprotein receptor (ASGPR), enhances potency of second-generation gapmer antisense oligonucleotides (ASOs) 6–10-fold in mouse liver. When combined with next-generation ASO designs comprised short S-cEt (S-2′-O-Et-2′,4′-bridged nucleic acid) ASOs, ∼60-fold enhancement relative to parent MOE (2′-O-methoxyethyl RNA) was observed. GN3-conjugated ASOs showed high affinity ASGPR,...
Abstract Background The p53 transcription factor is located at the core of a complex wiring signaling pathways that are critical for preservation cellular homeostasis. Only recently it has become clear regulates expression several long intergenic noncoding RNAs (lincRNAs). However, relatively little known about role lincRNAs play in this pathway. Results Here we characterize lincRNA named Pint (p53 induced transcript). We show ubiquitously expressed finely regulated by p53. In mouse cells,...
It is now obvious that the majority of cellular transcripts do not code for proteins, and a significant subset them are long non-coding RNAs (lncRNAs). Many lncRNAs show aberrant expression in cancer, some have been linked to cell transformation. However, underlying mechanisms remain poorly understood it unknown how sequences lncRNA dictate their function. Here we characterize function p53-regulated human LINC-PINT cancer. We find downregulated multiple types cancer acts as tumor suppressor...
Despite the inarguable relevance of p53 in cancer, genome-wide studies relating endogenous activity to expression lncRNAs human cells are still missing. Here, by integrating RNA-seq with ChIP-seq analyses a cancer cell line under DNA damage, we define high-confidence set 18 that transcriptional targets. We demonstrate two p53-regulated required for efficient binding some its target genes, modulating network and contributing apoptosis induction damage. also show p53-lncRNAs is lowered...
Spinal and bulbar muscular atrophy (SBMA) is caused by the polyglutamine androgen receptor (polyQ-AR), a protein expressed both lower motor neurons skeletal muscle. Although viewed as neuronopathy, data from patients mouse models suggest that muscle contributes to disease pathogenesis. Here, we tested this hypothesis using AR113Q knockin human bacterial artificial chromosome/clone (BAC) transgenic mice express full-length polyQ-AR display androgen-dependent weakness, atrophy, early death. We...
Transthyretin (TTR)-associated amyloidosis is a late-onset autosomal-dominant genetic disease. Over 100 amyloidogenic mutations have been identified in TTR which destabilize the tetramer thereby inducing formation of amyloid fibrils tissues such as heart and peripheral nerves. This disease mainly affects nerves, causing familial polyneuropathy (FAP) or heart, cardiomyopathy (FAC). Circulating predominantly produced by liver, only widely available clinical treatment for FAP orthotopic liver...
Advances in the medicinal chemistry of antisense oligonucleotide drugs have been instrumental achieving and optimizing activity cell types other than hepatocytes, type that is most sensitive to effects following systemic treatment. To broadly characterize on target messenger RNA (mRNA) levels different organs animals, we developed a situ hybridization technique using noncoding metastasis associated lung adenocarcinoma transcript 1 (MALAT1) as surrogate target. We used this evaluate...
African Americans develop end-stage renal disease at a higher rate compared with European due to 2 polymorphisms (G1 and G2 risk variants) in the apolipoprotein L1 (APOL1) gene common people of ancestry. Although this compelling genetic evidence provides an exciting opportunity for personalized medicine chronic kidney disease, drug discovery efforts have been greatly hindered by fact that APOL1 expression is lacking rodents. Here, we describe potentially novel physiologically relevant...
LncRNAs have been shown to be direct players in chromatin regulation, but little is known about their role at active genomic loci. We investigate the of lncRNAs gene activation by profiling RNA interactome SMARCB1-containing SWI/SNF complexes proliferating and senescent conditions. The isolation SMARCB1-associated transcripts, together with profiling, shows prevalent association regions where SMARCB1 differentially binds locally transcribed RNAs. identify SWINGN, a lncRNA interacting...
Abstract Aims Amyloidogenic transthyretin (ATTR) amyloidosis is a fatal disease characterized by progressive cardiomyopathy and/or polyneuropathy. AKCEA‐TTR‐L Rx (ION‐682884) ligand‐conjugated antisense drug designed for receptor‐mediated uptake hepatocytes, the primary source of circulating (TTR). Enhanced delivery pharmacophore expected to increase potency and support lower, less frequent dosing in treatment. Methods results demonstrated an approximate 50‐fold 30‐fold compared with...
Purpose: To preserve photoreceptor cell structure and function in a rodent model of retinitis pigmentosa with P23H rhodopsin by selective inhibition the mutant allele using second generation antisense oligonucleotide (ASO). Methods: Wild-type mice rats were treated ASO intravitreal (IVT) injection mRNA protein expression measured. Transgenic expressing murine gene (P23H transgenic rat Line 1) administered either mouse-specific or control ASO. The contralateral eye was injected PBS used as...
Abstract Centronuclear myopathies (CNM) are non-dystrophic muscle diseases for which no effective therapy is currently available. The most severe form, X-linked CNM, caused by myotubularin 1 ( MTM1 ) loss-of-function mutations, while the main autosomal dominant form due to dynamin2 DNM2 mutations. We previously showed that genetic reduction of expression in Mtm1 knockout (Mtm1KO) mice prevents development pathology. Here we show systemic delivery Dnm2 antisense oligonucleotides (ASOs) into...
Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disease that results from mutations in the alpha-1 (AAT) gene. The mutant AAT protein aggregates and accumulates liver leading to AATD disease, which only treatable by transplant. PiZ transgenic mouse strain expresses human (hAAT) transgene contains AATD-associated Glu342Lys mutation. mice exhibit many symptoms, including aggregates, increased hepatocyte death, fibrosis. In present study, we systemically treated with an antisense...
Rapid advances in the discovery of long noncoding RNAs (lncRNAs) have identified lineage- and cancer-specific biomarkers that may be relevant clinical management prostate cancer (PCa). Here we assembled analyzed a large RNA-seq dataset, from 585 patient samples, including benign tissue both localized metastatic PCa to discover validate differentially expressed genes associated with disease aggressiveness. We performed Sample Set Enrichment Analysis (SSEA) low versus high Gleason score...
The recessive genetic disease cystic fibrosis (CF) is caused by loss-of-function mutations in the CFTR (CF transmembrane conductance regulator) gene. Approximately 10% of patients with CF have at least one allele a nonsense mutation CFTR. Nonsense generate premature termination codons that can subject mRNA transcripts to rapid degradation through nonsense-mediated decay (NMD) pathway. Currently, there are no approved therapies specifically target Here, we identified antisense...
Depletion of Chop in pancreatic β cells optimizes insulin secretion and reduces fatty liver preclinical models.
Significance Centronuclear myopathies are rare and severe congenital muscle diseases. Here we hypothesized that reducing dynamin 2 (DNM2) may rescue the pathophysiology observed in DNM2 -related dominant centronuclear myopathy. The total expression was reduced a faithful murine model ( Dnm2 RW/+ mice) using two different methods targeting both mutated wild-type , adeno-associated virus-shRNA, or antisense oligonucleotides, leading to restoration of mass, histopathology, ultrastructural...
Article6 May 2021Open Access Source DataTransparent process HOTAIR lncRNA promotes epithelial–mesenchymal transition by redistributing LSD1 at regulatory chromatin regions Julien Jarroux ncRNA, Epigenetic and Genome Fluidity, CNRS UMR3244, Sorbonne Université, PSL University, Institut Curie, Centre de Recherche, Paris, FranceThese authors contributed equally to this work as first Search for more papers author Dominika Foretek orcid.org/0000-0002-2231-1710 Claire Bertrand Marc Gabriel France...
Hundreds of small nuclear non-coding RNAs, including nucleolar RNAs (snoRNAs), have been identified in different organisms, with important implications regulating gene expression and human diseases. However, functionalizing these mammalian cells remains challenging, due to methodological difficulties depleting especially snoRNAs. Here we report a convenient efficient approach deplete snoRNA, Cajal body RNA (scaRNA) mouse by conventional transfection chemically modified antisense...