A5076532068- RNA Interference and Gene Delivery
- Nanoparticle-Based Drug Delivery
- Animal Virus Infections Studies
- Nanoplatforms for cancer theranostics
- SARS-CoV-2 and COVID-19 Research
- Lipid Membrane Structure and Behavior
- Neonatal Respiratory Health Research
- Radiation Therapy and Dosimetry
- Nanopore and Nanochannel Transport Studies
- Viral gastroenteritis research and epidemiology
- Intraperitoneal and Appendiceal Malignancies
- Ovarian cancer diagnosis and treatment
- Virus-based gene therapy research
- Radiopharmaceutical Chemistry and Applications
- Advanced Polymer Synthesis and Characterization
- Inhalation and Respiratory Drug Delivery
- Veterinary medicine and infectious diseases
- Influenza Virus Research Studies
- Genomics and Chromatin Dynamics
- Neuroendocrine Tumor Research Advances
- Cancer therapeutics and mechanisms
- Nanotechnology research and applications
- Cystic Fibrosis Research Advances
- Bacteriophages and microbial interactions
- Synthesis of Tetrazole Derivatives
Sanofi (United States)
2021-2025
Translate Bio (United States)
2020-2022
Takeda (United States)
2016
University of North Carolina at Chapel Hill
2010-2014
Center for Translational Molecular Medicine
2014
Segeberger Kliniken
2014
UNC Lineberger Comprehensive Cancer Center
2011-2014
Rutgers, The State University of New Jersey
2012
University of North Carolina Health Care
2011
SUNY Polytechnic Institute
2009-2010
DNA-based gene therapy has considerable therapeutic potential, but the challenges associated with delivery continue to limit progress. Messenger RNA (mRNA) potential provide for transient production of proteins, without need nuclear and risk insertional mutagenesis. Here we describe sustained proteins in vivo both rodents non-human primates via nanoparticle-formulated mRNA. Nanoparticles formulated lipids lipid-like materials were developed two separate mRNA transcripts encoding either human...
One of the promises nanoparticle (NP) carriers is reformulation promising therapeutics that have failed clinical development due to pharmacologic challenges. However, current nanomedicine research has been focused on delivery established and novel therapeutics. Here we demonstrate proof principle using NPs revive potential abandoned compounds wortmannin (Wtmn) as a model drug. Wtmn potent inhibitor phosphatidylinositol 3' kinase-related kinases but translation drug-delivery We engineered NP...
Nanoparticle (NP) chemotherapeutics hold great potential as radiosensitizers. Their unique properties, such preferential accumulation in tumors and their ability to target through molecular targeting ligands, are ideally suited for radiosensitization. We aimed develop a molecularly targeted nanoparticle formulation of docetaxel (Dtxl) evaluate its property radiosensitizer. Using biodegradable biocompatible lipid-polymer NP platform folate ligand, we engineered folate-targeted (FT-NP) Dtxl....
Recent approval of mRNA vaccines for emergency use against COVID-19 is likely to promote rapid development mRNA-based targeting a wide range infectious diseases. Compared conventional approaches, this vaccine modality promises comparable potency while substantially accelerating the pace and deployment doses. Already demonstrated successfully single antigen such as COVID-19, technology could be optimized complex multi-antigen vaccines. Herein, utilizing multiple influenza antigens, we...
Abstract Emergency use authorization of COVID vaccines has brought hope to mitigate pandemic coronavirus disease 2019 (COVID-19). However, there remains a need for additional effective meet the global demand and address potential new viral variants. mRNA technologies offer an expeditious path alternative traditional vaccine approaches. Here we describe efforts utilize platform rational design evaluations candidates based on spike (S) glycoprotein SARS-CoV-2. Several constructs S-protein,...
Nanoparticles’ drug release kinetics can directly affect their therapeutic efficacy and toxicity.
Abstract Pulmonary delivery of mRNA via inhalation is a very attractive approach for RNA-based therapy treatment lung diseases. In this work, we have demonstrated successful development an mRNA-lipid nanoparticle (LNP) dry powder product (DPP), wherein the LNPs were spray dried using hydroalcoholic solvent along with mannitol and leucine as excipients. The desired critical attributes DPP accomplished by varying excipients, lipid composition, concentration LNPs, weight percentage mRNA....
Rational design and robust formulation processes are critical for optimal delivery of mRNA by lipid nanoparticles (LNPs). Varying degrees heterogeneity in mRNA-LNPs can affect their biophysical functional properties. Given the profound complexity mRNA-LNPs, it is to develop comprehensive orthogonal analytical techniques a better understanding these formulations. To this end, we developed ultracentrifugation method density-based separation subpopulations mRNA-LNPs. Four LNP formulations...
Lipid nanoparticles (LNPs) have shown great promise as delivery vehicles to transport messenger ribonucleic acid (mRNA) into cells and act vaccines for infectious diseases including COVID-19 influenza. The ionizable lipid incorporated within the LNP is known be one of main driving factors potency tolerability. Herein, we describe a novel family lipids synthesized with piperazine core derived from HEPES Good buffer. These unique asymmetric tails two dissimilar degradable moieties structure....
The basic principle of mRNA therapeutics involves delivery in vitro transcribed into a target cell, where cellular machinery translates the functional protein. In vaccine applications, an encoding viral protein will elicit protective immune response, whereas therapeutic absent (or dysfunctional) patient provides expression. Thus, mRNAs can be widely used development, replacement therapy, and treatment genetic diseases. Lipid nanoparticles (LNPs) are most common system being developed to...
Lipid nanoparticles (LNPs) have emerged as effective carriers for mRNA delivery in vaccine and therapeutic applications, attracting substantial attention since the COVID-19 pandemic. Continued efforts are crucial to optimize LNP composition improved efficacy elucidate underlying mechanisms driving differences protein expression. This study systematically screened PEGylated lipids intramuscular delivery, followed by optimization of formulation composition, physicochemical characterization,...
Summary An effective vaccine to address the global pandemic of coronavirus disease 2019 (COVID-19) is an urgent public health priority 1 . Novel synthetic mRNA and vector-based technologies offer expeditious development path alternative traditional approaches. Here we describe efforts utilize platform for rational design evaluations candidates based on Spike (S) glycoprotein Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), virus causing COVID-19. Several constructs expressing...
Heterogeneous lipid membranes tuned by pH were evaluated at 37 °C in the form of PEGylated vesicles composed pairs with dipalmitoyl (n = 16) and distearoyl 18) chain lengths. One type was chosen to have titratable moiety phosphatidic acid on its headgroup, other a phosphatidylcholine headgroup. The effect formation heterogeneities membrane permeability studied matching nonmatching increases decreasing either or Increased exhibited only Permeability rates correlate strongly predicted extent...
Aquilaria agallocha Roxb, family, Th ymelaeaceae, is an evergreen plant of India, China and Tibet, commonly described as aloe wood or agarwood. Traditionally, the bark, root heartwood are used for their medicinal properties a folk medicine to treat infl ammation, arthritis, vomiting, cardiac disorders, cough, asthma, leprosy, anorexia, headache gout. e present study was carried out investigate antioxidant activity ethyl acetate extract (EAA). EAA tested in vitro at diff erent concentrations...
The emergence of SARS-CoV-2 variants, especially Beta and Delta, has raised concerns about the reduced protection from previous infection or vaccination based on original Wuhan-Hu-1 (D614) virus. To identify promising regimens for inducing neutralizing titers towards new we evaluated monovalent bivalent mRNA vaccines either as primary a booster in nonhuman primates (NHPs). Two vaccines, D614-based MRT5500 Beta-based MRT5500β, tested sequential combination naïve NHPs produced modest to...
During direct cell-to-cell communication, lipids on the extracellular side of plasma membranes reorganize, and membrane-associated communication-related molecules colocalize. At colocalization sites, sometimes identified as rafts, local cell surface topography reactivity are altered. The processes regulating these changes largely unknown. On model lipid membranes, study simplified that control may potentially contribute to understanding related functions associated diseases. Integration...
Nanotechnology is a relatively new branch of science that involves harnessing the unique properties particles are nanometers in scale (nanoparticles). Nanoparticles can be engineered precise fashion where their size, composition and surface chemistry carefully controlled. This enables unprecedented freedom to modify some fundamental cargo, such as solubility, diffusivity, biodistribution, release characteristics immunogenicity. Since inception, nanoparticles have been utilized many areas...
Nanotechnology is a relatively new branch of science that involves harnessing the unique properties particles are nanometers in scale (nanoparticles). Nanoparticles can be engineered precise fashion where their size, composition and surface chemistry carefully controlled. This enables unprecedented freedom to modify some fundamental cargo, such as solubility, diffusivity, biodistribution, release characteristics immunogenicity. Since inception, nanoparticles have been utilized many areas...