A5015949636- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Lipid Membrane Structure and Behavior
- Advancements in Solid Oxide Fuel Cells
- Ion-surface interactions and analysis
- Protein Structure and Dynamics
- Retinal Development and Disorders
- Virus-based gene therapy research
- Atrial Fibrillation Management and Outcomes
- Supramolecular Self-Assembly in Materials
- AI in cancer detection
- Thyroid Cancer Diagnosis and Treatment
- Electrocatalysts for Energy Conversion
- Gut microbiota and health
- Catalytic Processes in Materials Science
- Clostridium difficile and Clostridium perfringens research
- RNA and protein synthesis mechanisms
- Cancer, Hypoxia, and Metabolism
- Thyroid Disorders and Treatments
- COVID-19 Clinical Research Studies
- COVID-19 Prevention and Impact
- Machine Learning in Healthcare
- Pharmacological Effects of Medicinal Plants
- Muscle Physiology and Disorders
- Lysosomal Storage Disorders Research
Bennett University
2024
SRM Institute of Science and Technology
2024
University of South Alabama Medical Center
2024
Decatur Memorial Hospital
2022-2024
Alabama College of Osteopathic Medicine
2024
Medical University of South Carolina
2023-2024
Oregon State University
2016-2022
D'Youville College
2021
Indian Institute of Science Bangalore
2013-2016
Nanyang Technological University
2013
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...
Lipid nanoparticle (LNP) packaged mRNA vaccines have been deployed against infectious diseases such as COVID-19, yet their structural features remain unclear. Cholesterol, a major constituent within LNPs, contributes to morphology that influences gene delivery. Herein, we examine the structure of LNPs containing cholesterol derivatives using electron microscopy, differential scanning calorimetry, and membrane fluidity assays. formulated with C24 alkyl show polymorphic shape various degrees...
The promise of gene therapy for the treatment cystic fibrosis has yet to be fully clinically realized despite years effort toward correcting underlying genetic defect in transmembrane conductance regulator (CFTR). mRNA via nanoparticle delivery represents a powerful technology transfer material cells with large, widespread populations, such as airway epithelia. We deployed relevant lipid-based (LNP) packaging and large chemically modified CFTR (cmCFTR) patient-derived bronchial epithelial...
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...
Residue depth accurately measures burial and parameterizes local protein environment. Depth is the distance of any atom/residue to closest bulk water. We consider non-bulk waters occupy cavities, whose volumes are determined using a Voronoi procedure. Our estimation cavity sizes statistically superior estimates made by CASTp VOIDOO, on par with McVol over data set 40 cavities. calculated correlated best experimentally destabilization 34 mutants from five proteins. Some cavities identified...
Gene therapy is now an effective approach to treat many forms of retinal degeneration. Delivery agents that are cell-specific, allow for multiple dosing regimens, and have low immunogenicity needed expand the utility gene retina. We generated eight novel lipid nanoparticles (LNPs) ranging in size from 50 nm 150 by changing PEG content 5% 0.5%, respectively. Subretinal injections LNP-mRNA encoding luciferase revealed 0.5% within elicits highest expression. Similar LNP delivered cre mRNA into...
Understanding how mutations affect protein activity and organismal fitness is a major challenge. We used saturation mutagenesis combined with deep sequencing to determine mutational sensitivity scores for 1,664 single-site mutants of the 101 residue Escherichia coli cytotoxin, CcdB at seven different expression levels. Active-site residues could be distinguished from buried ones, based on their differential tolerance aliphatic charged amino acid substitutions. At nonactive-site positions,...
Abstract 2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), fatal neurodegenerative disorder that stems from abnormal accumulation in the endo/lysosomes. Unfortunately, extremely high doses HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence poly (ethylene glycol)...
Lipid nanoparticle-RNA formulations are used for the delivery of vaccines and other therapies. RNA molecules encapsulated within their interior through electrostatic interactions with positively charged lipids. The identity lipids that present at surface play a role in how they interact perceived by body resultant potency. To investigate chemistry two we develop cryogenic sample preparation transmission electron microscopy (TEM) prior to depth profiling Orbitrap secondary ion mass...
Lipid nanoparticle RNA (LNP-RNA) formulations are used for the delivery of vaccines and other therapies. molecules encapsulated within their interior through electrostatic interactions with positively charged lipids. The identity lipids that present at surface play a role in how they interact perceived by body resultant potency. We use model formulation to develop cryogenic sample preparation molecular depth profiling Orbitrap secondary ion mass spectrometry (Cryo-OrbiSIMS) preceded...
Lipid nanoparticle RNA (LNP-RNA) formulations are used for the delivery of vaccines and other therapies. molecules encapsulated within their interior through electrostatic interactions with positively charged lipids. The identity lipids that present at surface play a role in how they interact perceived by body resultant potency. Here, we use model formulation to develop cryogenic sample preparation molecular depth profiling Orbitrap secondary ion mass spectrometry (Cryo-OrbiSIMS) preceded...
Abstract This study presents the first messenger RNA (mRNA) therapy for metastatic ovarian cancer and cachexia‐induced muscle wasting based on lipid nanoparticles that deliver follistatin (FST) mRNA predominantly to clusters following intraperitoneal administration. The secreted FST protein, endogenously synthesized from delivered mRNA, efficiently reduces elevated activin A levels associated with aggressive cachexia. By altering cell phenotype, treatment prevents malignant ascites, delays...
Direct oral anticoagulants (DOACs), such as apixaban, are used for the prevention and management of thromboembolic diseases. Here, we present a case 72-year-old African American woman who presented to hospital with shortness breath precordial chest pain three days. The patient was diagnosed volume overload associated progression chronic kidney disease (CKD) subsequently admitted hospital. Since failed adequately respond diuretics, hemodialysis initiated. During stay, she developed paroxysmal...
This study explores cofiring ceria (CeO2) with NiO and 8 mol% yttria-stabilized zirconia (YSZ) to form Ni-based cermet anodes for high-temperature solid oxide fuel cells (SOFCs) operating on syngas n-butane/steam feeds. Particular attention is paid the suppression of carbon deposit growth in carbonaceous CeO2 was cofired YSZ a porous Ni anode support layer after reduction H2 at 800°C. The (1 mm thick) combined Ni/YSZ functional (∼25 μm thick), dense electrolyte (10–20 La0.8Sr0.2MnO3−x...