A5061695047- Cell Adhesion Molecules Research
- RNA Interference and Gene Delivery
- Phytochemistry and Biological Activities
- Plasma Applications and Diagnostics
- Phytochemicals and Antioxidant Activities
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Cancer and biochemical research
- Respiratory Support and Mechanisms
- Cellular Mechanics and Interactions
- Chronic Kidney Disease and Diabetes
- Monoclonal and Polyclonal Antibodies Research
- Natural product bioactivities and synthesis
- Essential Oils and Antimicrobial Activity
- Plant tissue culture and regeneration
- Liver Disease Diagnosis and Treatment
- Fungal Biology and Applications
- Magnetic and Electromagnetic Effects
- Cancer Cells and Metastasis
- Lipid Membrane Structure and Behavior
- Electromagnetic Fields and Biological Effects
- Lichen and fungal ecology
- Food Quality and Safety Studies
- Botany and Plant Ecology Studies
- Advanced biosensing and bioanalysis techniques
- Immunotherapy and Immune Responses
Moderna Therapeutics (United States)
2017-2024
National Institute of Research and Development for Biological Sciences
2010-2024
Grigore T. Popa University of Medicine and Pharmacy
2013-2023
Alexandru Ioan Cuza University
2011-2018
The Ohio State University
2005-2016
Yahoo (United Kingdom)
2016
Environmental Molecular Sciences Laboratory
2013-2015
Pacific Northwest National Laboratory
2012-2015
McGill University
2014
The Ohio State University Wexner Medical Center
2013
mRNA vaccines have the potential to tackle many unmet medical needs that are unable be addressed with conventional vaccine technologies. A potent and well-tolerated delivery technology is integral fully realizing of vaccines. Pre-clinical clinical studies demonstrated delivered intramuscularly (IM) first-generation lipid nanoparticles (LNPs) generates robust immune responses. Despite progress made over past several years, there remains significant opportunity for improvement, as most...
Endosomal sequestration of lipid-based nanoparticles (LNPs) remains a formidable barrier to delivery. Herein, structure-activity analysis cholesterol analogues reveals that incorporation C-24 alkyl phytosterols into LNPs (eLNPs) enhances gene transfection and the length tail, flexibility sterol ring polarity due -OH group is required maintain high transfection. Cryo-TEM displays polyhedral shape for eLNPs compared spherical LNPs, while x-ray scattering shows little disparity in internal...
Isolated methylmalonic acidemia/aciduria (MMA) is a devastating metabolic disorder with poor outcomes despite current medical treatments. Like other mitochondrial enzymopathies, enzyme replacement therapy (ERT) not available, and although promising, AAV gene can be limited by pre-existing immunity has been associated genotoxicity in mice. To develop new class of for MMA, we generated pseudoU-modified codon-optimized mRNA encoding human methylmalonyl-CoA mutase (hMUT), the most frequently...
Intracellular delivery of mRNA holds great potential for vaccine1−3 and therapeutic4 discovery development. Despite increasing recognition the utility lipid-based nanoparticles (LNPs) intracellular mRNA, particle engineering is hindered by insufficient understanding endosomal escape, which believed to be a main limiter cytosolic availability activity nucleic acid inside cell. Using series CRISPR-based genetic perturbations lysosomal pathway, we have identified that late endosome/lysosome...
Propionic acidemia/aciduria (PA) is an ultra-rare, life-threatening, inherited metabolic disorder caused by deficiency of the mitochondrial enzyme, propionyl-CoA carboxylase (PCC) composed six alpha (PCCA) and beta (PCCB) subunits. We herein report enzyme replacement approach to treat PA using a combination two messenger RNAs (mRNAs) (dual mRNAs) encoding both human PCCA (hPCCA) PCCB (hPCCB) encapsulated in biodegradable lipid nanoparticles (LNPs) produce functional PCC liver. In patient...
Abstract Accelerated blood clearance (ABC) is a phenomenon in which certain pharmaceutical agents are rapidly cleared from the upon second and subsequent administrations. ABC has been observed for many lipid-delivery vehicles, including liposomes lipid nanoparticles (LNP). Previous studies have demonstrated role humoral responses against polyethylene glycol motifs clearance, but significant gaps remain our understanding of mechanism ABC, strategies limiting impact clinical setting elusive....
Atmospheric pressure DC-driven self-pulsing transient spark (TS) discharge operated in air and pulse-driven dielectric barrier plasma jet (PJ) helium contact with water solutions were used for inducing chemical effects solutions, the treatment of bacteria (Escherichia coli), mammalian cells (Vero line normal cells, HeLa cancerous cells), deoxyribonucleic acid (dsDNA), protein (bovine serum albumin). Two different methods solution supply TS: electrode system spray system. The both TS systems...
Citrin deficiency is an autosomal recessive disorder caused by loss-of-function mutations in SLC25A13, encoding the liver-specific mitochondrial aspartate/glutamate transporter. It has a broad spectrum of clinical phenotypes, including life-threatening neurological complications. Conventional protein replacement therapy not option for these patients because drug delivery hurdles, and current gene approaches (e.g., AAV) have been hampered immunogenicity genotoxicity. Although dietary shown...
Abstract Glycogen Storage Disease 1a (GSD1a) is a rare, inherited metabolic disorder caused by deficiency of glucose 6-phosphatase (G6Pase-α). G6Pase-α critical for maintaining interprandial euglycemia. GSD1a patients exhibit life-threatening hypoglycemia and long-term liver complications including hepatocellular adenomas (HCAs) carcinomas (HCCs). There no treatment the current standard-of-care managing (Glycosade ® /modified cornstarch) fails to prevent HCA/HCC risk. Therapeutic modalities...
Topical liposomal drug formulations containing AS1411-aptamer conjugated liposomes were designed to deliver in a sustained way the 5-fluorouracil tumor site but also increase compliance of patients with basal cell carcinoma. The penetrability efficiency through Strat-M membrane and skin irritation potential obtained topical evaluated vitro Korsmeyer Peppas equation was considered as most appropriate model release. Additionally, cytostatic activity for targeted antitumor therapy hemolytic...
Airborne nanoparticles (NPs) that enter the respiratory tract are likely to reach alveolar region. Accumulating observations support a role for zinc oxide (ZnO) NP dissolution in toxicity, but majority of in-vitro studies were conducted cells exposed NPs growth media, where large doses dissolved ions shed into exposure solution. To determine precise intracellular accumulation dynamics and fate (Zn2+) by airborne cellular environment, we epithelial aerosolized at air–liquid interface (ALI)....
Cell migration plays a central role in the invasion and metastasis of tumors. As cells leave primary tumor, they undergo an epithelial to mesenchymal transition (EMT) migrate as single cells. Epithelial tumor may also highly directional manner collective group some settings. We previously discovered that myoferlin (MYOF) is overexpressed breast cancer depletion MYOF results (MET) reduced through extracellular matrix (ECM). However, biomechanical mechanisms governing cell motility during are...
Extremely low frequency electromagnetic fields aren't considered as a real carcinogenic agent despite the fact that some studies have showed impairment of DNA integrity in different cells lines. The aim this study was evaluation late effects 100 Hz and 5.6 mT field, applied continuously or discontinuously, on Vero assessed by alkaline Comet assay cell cycle analysis. Normal were exposed to extremely (100 Hz, mT) for 45 minutes. analysis performed 48 hours after treatment. Exposed samples...
The emergence of pathogenic multidrug-resistant bacteria demands new approaches in finding effective antibacterial agents. Synthetic flavonoids could be a reliable solution due to their important antimicrobial activity. We report here the potent vitro activity ClCl-flav—a novel synthetic tricyclic flavonoid. effects were tested using minimum inhibitory concentration (MIC), time kill and biofilm formation assays. Fluorescence microscopy scanning electron employed study mechanism action. MTT...