A5002641644- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- MicroRNA in disease regulation
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Extracellular vesicles in disease
- DNA and Nucleic Acid Chemistry
- Genetic Neurodegenerative Diseases
- Liver Disease Diagnosis and Treatment
- RNA regulation and disease
- Liver physiology and pathology
- Neurogenetic and Muscular Disorders Research
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Mitochondrial Function and Pathology
- Bacteriophages and microbial interactions
- Liver Diseases and Immunity
- Muscle Physiology and Disorders
- Neurological disorders and treatments
- Lipid Membrane Structure and Behavior
- Genomics and Phylogenetic Studies
- Bacterial Genetics and Biotechnology
- Cancer, Hypoxia, and Metabolism
University of Massachusetts Chan Medical School
2015-2024
Massachusetts Academy of Math and Science
2024
UMass Memorial Medical Center
2023-2024
Chita State Academy of Medicine
2024
NeuroNexus (United States)
2023
The University of Sydney
2023
University of Massachusetts System
2019
University of Worcester
2017
Institute of Molecular Medicine
2017
Phio Pharmaceuticals (United States)
2009-2013
Transfected siRNAs regulate numerous transcripts sharing limited complementarity to the RNA duplex. This unintended ("off-target") silencing can hinder use of RNAi define gene function. Here we describe position-specific, sequence-independent chemical modifications that reduced partially complementary by all tested. Silencing perfectly matched targets was unaffected these modifications. The modification also off-target phenotypes in growth inhibition studies. Key 2'-O-methyl ribosyl...
Extracellular vesicles (EVs), including exosomes and microvesicles (MVs), are explored for use in diagnostics, therapeutics drug delivery. However, little is known about the relationship of protein lipid composition EVs their source cells. Here, we report high-resolution lipidomic proteomic analyses MVs derived by differential ultracentrifugation from 3 different cell types: U87 glioblastoma cells, Huh7 hepatocellular carcinoma cells human bone marrow-derived mesenchymal stem (MSCs). We...
Although recent microarray studies have provided evidence of RNA interference (RNAi)-mediated off-target gene modulation, little is known about whether these changes induce observable phenotypic outcomes. Here we show that a fraction randomly selected small inhibitory RNAs (siRNAs) can in cell viability target-independent fashion. The observed toxicity requires an intact RNAi pathway and be eliminated by the addition chemical modifications reduce effects. Furthermore, analysis toxic nontoxic...
To identify proteins that participate in clathrin-mediated endocytosis of the epidermal growth factor receptor (EGFR), 13 endocytic were depleted HeLa cells using highly efficient small interfering RNAs designed a novel selection algorithm. The effects on ligand-induced EGFR compared with those constitutive internalization transferrin receptor. knock-downs clathrin heavy chain and dynamin produced maximal inhibitory both receptors. Depletion α, β2, or μ2 subunits AP-2 reduced EGF rates by...
Delivery represents a significant barrier to the clinical advancement of oligonucleotide therapeutics for treatment neurological disorders, such as Huntington's disease. Small, endogenous vesicles known exosomes have potential act delivery vehicles, but robust and scalable methods loading RNA therapeutic cargo into are lacking. Here, we show that hydrophobically modified small interfering RNAs (hsiRNAs) efficiently load upon co-incubation, without altering vesicle size distribution or...
Exosomes can deliver therapeutic RNAs to neurons. The composition and the safety profile of exosomes depend on type exosome-producing cell. Mesenchymal stem cells are considered be an attractive cell for exosome production. However, scalable methods isolate manufacture from mesenchymal lacking, a limitation clinical translation technology. We evaluate different sources find that umbilical cord-derived produce highest yield. To optimize production, we cultivate in microcarrier-based...
Long (27–29-bp dsRNA) Dicer-dependent substrates have been identified as potent mediators of RNAi-induced gene knockdown in HEK293 and HeLa cells. As the lengths these molecules are reported to be below threshold generally regarded necessary for induction mammalian interferon (IFN) response, long siRNA being considered RNAi both research therapeutic settings. In this report, we demonstrate that >23-bp dsRNA can influence cell viability induce a IFN response (highlighted by strong...
RNA interference represents an exciting new technology that could have therapeutic applications for the treatment of viral infections. Hepatitis C virus (HCV) is a major cause chronic liver disease and affects >270 million individuals worldwide. The HCV genome single-stranded functions as both messenger replication template, making it attractive target study interference. Double-stranded small interfering (siRNA) molecules designed to were introduced through electroporation into human...
Dicer processes long double-stranded RNA (dsRNA) and pre-microRNAs to generate the functional intermediates (short interfering RNAs microRNAs) of interference pathway. Here we identify features structure that affect specificity efficiency. The data presented show various attributes 3′ end structure, including overhang length sequence composition, play a primary role in determining position cleavage both dsRNA unimolecular, short hairpin (shRNA). We also demonstrate siRNA affects overall...
The hammerhead ribozyme is a small RNA motif that catalyzes the cleavage and ligation of RNA. well-studied minimal inactive under physiological conditions requires high Mg(2+) concentrations for efficient cleavage. In contrast, natural hammerheads are active contain motifs outside catalytic core lower requirement Mg(2+). Single-turnover kinetics were used here to characterize pH dependence trans-cleaving construct Schistosoma mansoni ribozyme. Compared motif, 100-fold less achieve rate 1...
Another drug class may soon be added to cholesterol-lowering strategies: a chemically modified, small interfering RNA conjugated the trivalent N-acetylgalactosamine. The siRNAs are oligonucleotide therapeutics, which destroy before protein is synthesized.