A5044803370- RNA Interference and Gene Delivery
- Organometallic Complex Synthesis and Catalysis
- Advanced biosensing and bioanalysis techniques
- Biofuel production and bioconversion
- Virus-based gene therapy research
- Proteins in Food Systems
- Pickering emulsions and particle stabilization
- Surfactants and Colloidal Systems
- Inorganic and Organometallic Chemistry
- Asymmetric Hydrogenation and Catalysis
- Microbial Metabolic Engineering and Bioproduction
- Synthesis and characterization of novel inorganic/organometallic compounds
- Molecular Junctions and Nanostructures
- Synthetic Organic Chemistry Methods
- Microbial Inactivation Methods
- Listeria monocytogenes in Food Safety
- Immunotherapy and Immune Responses
- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- Ferrocene Chemistry and Applications
- Nanoparticle-Based Drug Delivery
- Catalysis for Biomass Conversion
- MicroRNA in disease regulation
- Radioactive element chemistry and processing
- Enzyme Production and Characterization
Johns Hopkins University
2015-2024
Johns Hopkins Medicine
2015-2024
Dow Chemical (United States)
1999-2024
Avidea Technologies (United States)
2024
Integrated BioTherapeutics (United States)
2024
Tampa General Hospital
2022
University of South Florida
2022
Syracuse University
2013-2019
Kennedy Krieger Institute
2018
Norwich Research Park
2000-2017
Biodegradable polymeric nanoparticles have the potential to be safer alternatives viruses for gene delivery; however, their use has been limited by poor efficacy in vivo. In this work, we synthesize and characterize delivery evaluate DNA of herpes simplex virus type I thymidine kinase (HSVtk) combined with prodrug ganciclovir (GCV) a malignant glioma model. We investigated polymer structure two rat cell lines, 9L F98, discover nanoparticle formulations more effective than leading commercial...
Efficient cytosolic protein delivery is necessary to fully realize the potential of therapeutics. Current methods often suffer from low serum tolerance and limited in vivo efficacy. Here, we report synthesis validation a previously unreported class carboxylated branched poly(β-amino ester)s that can self-assemble into nanoparticles for efficient intracellular variety different proteins. In vitro, enabled rapid cellular uptake, endosomal escape, functional release cells media containing 10%...
Quantitative bioassay enables the development of next-generation biodegradable polymeric nanoparticles for in vivo mRNA delivery.
Senescent cells (SnCs) are increasingly recognized as central effector in age-related pathologies. Extracellular vesicles (EVs) potential cellular communication tools through which SnCs exert functions the local tissue environment. To test this hypothesis a medical indication that could be validated clinically, we evaluated EV production from enriched chondrocytes isolated human arthritic cartilage. increased dose-responsive manner concentration of increased. The EVs were capable...
Despite our growing molecular-level understanding of glioblastoma (GBM), treatment modalities remain limited. Recent developments in the mechanisms cell fate regulation and nanomedicine provide new avenues by which to treat manage brain tumors via delivery molecular therapeutics. Here, we have developed bioreducible poly(β-amino ester) nanoparticles that demonstrate high intracellular efficacy, low cytotoxicity, escape from endosomes, promotion cytosol-targeted environmentally triggered...
A fundamental goal of second generation ethanol production is to increase the concentration 10% (v/v) or more optimise distillation costs. Semi simultaneous saccharification and fermentations (SSSF) were conducted at small pilot scale (5L) utilising fed-batch additions solid shredded copier paper substrate. Early addition Accellerase® 1500 16 FPU/g substrate 30 U/g β-glucosidase followed by only batch allowed low final equivalent enzyme concentrations be achieved (3.7 substrate) whilst...
Pretreatments are a prerequisite for enzymatic hydrolysis of biomass and production ethanol. They considered to open up the plant cell wall structure by altering, moving or solubilizing lignin hydrolyzing proportion hemicellulosic moieties. However, there is little information concerning pretreatment-induced changes on wheat bran polymers indeed in phenolic esters other lignocellulosic biomass. Here, we evaluate polymeric (chemical physical) as result selected hydrothermal pretreatment...
Triggering shape-memory functionality under clinical hyperthermia temperatures could enable the control and actuation of systems in practice. For this purpose, we developed light-inducible microparticles composed a poly(d,l-lactic acid) (PDLLA) matrix encapsulating gold nanoparticles (Au@PDLLA hybrid microparticles). This polymeric system for first time demonstrates capability maintaining an anisotropic shape at body temperature with triggered effect back to spherical narrow range above...
Functional codelivery of plasmid DNA and RNA oligonucleotides in the same nanoparticle system is challenging due to differences their physical properties as well intracellular locations function. In this study, we synthesized a series reducible branched ester-amine quadpolymers (rBEAQs) investigated ability coencapsulate deliver plasmids oligos. The rBEAQs are designed leverage polymer branching, reducibility, hydrophobicity successfully cocomplex nanoparticles at low nucleic acid w/w ratios...
The CRISPR-Cas9 system is a powerful gene-editing tool with wide-ranging applications, but the safe and efficient intracellular delivery of CRISPR components remains challenge. In this study, we utilized biodegradable poly(beta-amino ester) nanoparticles to codeliver plasmid DNA encoding Cas9 short guide RNA (sgRNA), respectively, enable gene knockout following CRISPR-mediated cleavage at one genomic site (1-cut edit), as well deletion two sites flanking region interest (2-cut edits). We...
Clinical translation of polymer-based nanocarriers for systemic delivery RNA has been limited due to poor colloidal stability in the blood stream and intracellular cytosol. To address these limitations, this study reports a new strategy incorporating photocrosslinking bioreducible nanoparticles improved extracellularly rapid release intracellularly. In design, polymeric contain ester bonds hydrolytic degradation disulfide environmentally triggered small interfering (siRNA) These...
Abstract In the last decade, there has been a tremendous increase in number of reports on transition metal complex-mediated butadiene homo- and copolymerization. While typical classical titanium, nickel, cobalt, neodymium based catalysts have almost exclusively applied to production high cis-1,4-polybutadiene, alternative catalyst systems are currently being developed which enable tuning polybutadiene microstructure permit defined changes polymer properties such as molecular weight...
SIRT6 is a histone deacetylase that has been proposed as potential therapeutic target for metabolic disorders and the prevention of age-associated diseases. Thus, identification compounds modulate activity could be great importance. The aim this study was to develop screening method novel modulators from natural plant extract. We immobilized onto surface magnetic beads, assessed enzymatic on synthetic acetylated tails (H3K9Ac) by measuring products deacetylation process. coated beads were...
Rice cultivation produces two waste streams, straw and husk, which could be exploited more effectively. Chemical pretreatment studies using rice residues have largely focussed on exploitation alone, often at low substrate concentrations. Moreover, it is currently not known how the recalcitrant residue, responds to steam explosion without addition of chemicals.The aim this study has been systematically compare effects severity enzymatic saccharification simultaneous fermentation husk produced...
Abstract Translation of biomaterial‐based nanoparticle formulations to the clinic faces significant challenges including efficacy, safety, consistency and scale‐up manufacturing, stability during long‐term storage. Continuous microfluidic fabrication polymeric nanoparticles has potential alleviate associated with manufacture, while offering a scalable solution for clinical level production. Poly(beta‐amino esters) (PBAE)s are class biodegradable cationic polymers that self‐assemble anionic...
Significance There is an urgent need for improved cancer immunotherapies. The nanoparticles described here deliver genes to stimulate the immune system specifically kill tumor cells. This synthetic, biodegradable avoids use of common gene delivery materials like viruses that can have safety concerns and manufacturing limitations. Local nanoparticle evades adverse side effects stemming from systemic administration immune-activating therapeutics. Importantly, this technology causes a...
Chromium complexes with bis(phospholane) ligands were synthesized and evaluated for ethylene tetramerization in a high-throughput reactor. Three ligand parameters—the phospholane substituent, the backbone, type of phosphine (cyclic vs acyclic)—were investigated. The size substituent was found to impact selectivity resulting catalysts, smaller substituents leading production larger proportions 1-octene. Changing backbone from 1,2-phenylene did not catalysis, but use acyclic phosphines place...
Suprachoroidal nonviral gene therapy with biodegradable poly(β-amino ester) nanoparticles (NPs) provides widespread expression in photoreceptors and retinal pigmented epithelial (RPE) cells therapeutic benefits rodents. Here, we show a human-sized minipig eye that suprachoroidal injection of 50 μl NPs containing 19.2 μg GFP plasmid caused RPE throughout the entire no toxicity. Two weeks after 50, 100, or 200 μl, there was considerable within-eye between-eye variability reduced 3 months...