Lipid-Coated Mesoporous Silica Nanoparticles for Targeted Drug Delivery Across the Blood-Brain Barrier
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Choudhary, Hemant↗
Engineering topics
Branda, Steven
Publications and source records attributed to Branda, Steven.
Reconfiguration of the Respiratory Tract Microbiome to Prevent and Treat Burkholderia Infection
New approaches to preventing and treating infections, particularly of the respiratory tract, are needed. One promising strategy is to reconfigure microbial communities (microbiomes) within the host to improve defense against pathogens. Probiotics and prebiotics for gastrointestinal (GI) infections offer a template for success. We sought to develop comparable countermeasures for respiratory infections. First, we characterized interactions between the airway microbiome and a biodefense-related respiratory pathogen ( Burkholderia thailandensis ; Bt), using a mouse model of infection. Then, we recovered microbiome constituents from the airway and assessed their ability to re-colonize the airway and protect against respiratory Bt infection. We found that microbiome constituents belonging to Bacillus and related genuses frequently displayed colonization and anti-Bt activity. Comparative growth requirement profiling of these Bacillus strains vs Bt enabled identification of candidate prebiotics. This work serves as proof of concept for airway probiotics, as well as a strong foundation for development of airway prebiotics.
59 BASIC BIOLOGICAL SCIENCES↗
Nanoparticle Mediated Delivery of Therapeutic mRNA for Protection Against Lung Damage
Medical countermeasures (MCMs) based on messenger ribonucleic acid (mRNA) are promising due to their programmability, targeting precision and specificity, predictable physicochemical properties, and amenability to scalable manufacture. However, safe and effective delivery vehicles are needed, especially for targeting the lung. We developed a generalized approach to nanoparticle-mediated mRNA delivery to lung, and used it to evaluate candidate therapies. In initial studies, reporter mRNA was delivered using lipid-coated mesoporous silica nanoparticles (LC-MSNs) and lipid nanoparticles (LNPs), the latter with greater consistency. Then, mRNA encoding known protein therapies were delivered using LNPs. These formulations showed some toxicity in mice with lung damage, but those with IL-1RA, sACE2-Ig, and ANGPT1 mRNA were modestly therapeutic on balance. Our work advances the state of the art for mRNA delivery to lung, and provides a foundation for evaluating and characterizing mRNA-based lung therapies, including three that appear to be exceptionally promising.
59 BASIC BIOLOGICAL SCIENCES↗
Therapeutic phages and methods thereof
The present invention relates, in part, to engineered viruses (e.g., engineered phages), phage cocktails, and methods of producing and/or identifying viruses for targeting pathogenic bacteria.
Williams, Kelly Porter↗
Augmentation of Antibacterial Activity in Mesenchymal Stromal Cells Through Systems-Level Analysis and CRISPR-mediated Activation of CD14.
Abstract not provided.
Hirakawa, Matthew↗