Jacob W. Myerson
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View article: Targeted lipid nanoparticles containing IL-10 mRNA improve outcomes in experimental intracerebral hemorrhage
Targeted lipid nanoparticles containing IL-10 mRNA improve outcomes in experimental intracerebral hemorrhage Open
Intracerebral hemorrhage (ICH) is a lethal and highly morbid form of stroke for which there is no disease-specific therapy. Inflammation after ICH is an important mechanism of secondary damage, and the inflamed endothelium in ICH is a prom…
View article: Limiting endosomal damage sensing reduces inflammation triggered by lipid nanoparticle endosomal escape
Limiting endosomal damage sensing reduces inflammation triggered by lipid nanoparticle endosomal escape Open
View article: Tropomyosin 1 promotes platelet adhesion and clot contraction separate from its roles in developmental hematopoiesis
Tropomyosin 1 promotes platelet adhesion and clot contraction separate from its roles in developmental hematopoiesis Open
Genome-wide associations studies (GWAS) have linked the Tropomyosin 1 ( Tpm1 ) gene locus to quantitative blood trait variation, but related mechanisms are unclear. Tpm1 encodes an actin-binding protein that stabilizes actin filaments and …
View article: Targeting DNA-LNPs to Endothelial Cells Improves Expression Magnitude, Duration, and Specificity
Targeting DNA-LNPs to Endothelial Cells Improves Expression Magnitude, Duration, and Specificity Open
DNA-lipid nanoparticles (DNA-LNPs) loaded with inhibitors of the cGAS-STING pathway enable safe and effective delivery of DNA in vivo . Herein, we report the first instances of extrahepatic DNA-LNP targeting. DNA-LNPs conjugated to antibod…
View article: VCAM-Targeted Nanocarriers: Transforming the Brain's Vasculature into a Therapeutic Biofactory
VCAM-Targeted Nanocarriers: Transforming the Brain's Vasculature into a Therapeutic Biofactory Open
View article: A percolation phase transition controls complement protein coating of surfaces
A percolation phase transition controls complement protein coating of surfaces Open
View article: Targeted lipid nanoparticles containing IL-10 mRNA improve outcomes in experimental intracerebral hemorrhage
Targeted lipid nanoparticles containing IL-10 mRNA improve outcomes in experimental intracerebral hemorrhage Open
View article: Conjugation Chemistry Markedly Impacts Toxicity and Biodistribution of Targeted Nanoparticles, Mediated by Complement Activation
Conjugation Chemistry Markedly Impacts Toxicity and Biodistribution of Targeted Nanoparticles, Mediated by Complement Activation Open
Conjugation chemistries are a major enabling technology for the development of drug delivery systems, from antibody‐drug conjugates to antibody‐targeted lipid nanoparticles inspired by the success of the COVID‐19 vaccine. However, here it …
View article: Multi-stage-mixing to control the supramolecular structure of lipid nanoparticles, thereby creating a core-then-shell arrangement that improves performance by orders of magnitude
Multi-stage-mixing to control the supramolecular structure of lipid nanoparticles, thereby creating a core-then-shell arrangement that improves performance by orders of magnitude Open
As they became the dominant gene therapy platform, lipid nanoparticles (LNPs) experienced nearly all their innovation in varying the structure of individual molecules in LNPs. This ignored control of the spatial arrangement of molecules, w…
View article: A percolation-type criticality threshold controls immune protein coating of surfaces
A percolation-type criticality threshold controls immune protein coating of surfaces Open
When a material enters the body, it is immediately attacked by hundreds of proteins, organized into complex networks of binding interactions and reactions. How do such complex systems interact with a material, “deciding” whether to attack?…
View article: Nanocarriers' repartitioning of drugs between blood subcompartments as a mechanism of improving pharmacokinetics, safety, and efficacy
Nanocarriers' repartitioning of drugs between blood subcompartments as a mechanism of improving pharmacokinetics, safety, and efficacy Open
View article: Marginated Neutrophils in the Lungs Effectively Compete for Nanoparticles Targeted to the Endothelium, Serving as a Part of the Reticuloendothelial System
Marginated Neutrophils in the Lungs Effectively Compete for Nanoparticles Targeted to the Endothelium, Serving as a Part of the Reticuloendothelial System Open
Nanomedicine has long pursued the goal of targeted delivery to specific organs and cell types but has yet to achieve this goal with the vast majority of targets. One rare example of success in this pursuit has been the 25+ years of studies…
View article: Marginated neutrophils in the lungs effectively compete for nanoparticles targeted to the endothelium, serving as a part of the reticuloendothelial system
Marginated neutrophils in the lungs effectively compete for nanoparticles targeted to the endothelium, serving as a part of the reticuloendothelial system Open
Nanomedicine has long pursued the goal of targeted delivery to specific organs and cell types but has not achieved this goal with the vast majority of targets. One rare example of success in this pursuit has been the 25+ years of studies t…
View article: Lipid Nanoparticle-Associated Inflammation is Triggered by Sensing of Endosomal Damage: Engineering Endosomal Escape Without Side Effects
Lipid Nanoparticle-Associated Inflammation is Triggered by Sensing of Endosomal Damage: Engineering Endosomal Escape Without Side Effects Open
Lipid nanoparticles (LNPs) have emerged as the dominant platform for RNA delivery, based on their success in the COVID-19 vaccines and late-stage clinical studies in other indications. However, we and others have shown that LNPs induce sev…
View article: Targeting lipid nanoparticles to the blood-brain barrier to ameliorate acute ischemic stroke
Targeting lipid nanoparticles to the blood-brain barrier to ameliorate acute ischemic stroke Open
View article: Physicochemical Targeting of Lipid Nanoparticles to the Lungs Induces Clotting: Mechanisms and Solutions
Physicochemical Targeting of Lipid Nanoparticles to the Lungs Induces Clotting: Mechanisms and Solutions Open
Lipid nanoparticles (LNPs) have become the dominant drug delivery technology in industry, holding the promise to deliver RNA to up or down‐regulate any protein of interest. LNPs have mostly been targeted to specific cell types or organs by…
View article: A combination of physicochemical tropism and affinity moiety targeting of lipid nanoparticles enhances organ targeting
A combination of physicochemical tropism and affinity moiety targeting of lipid nanoparticles enhances organ targeting Open
Two camps have emerged in the targeting of nanoparticles to specific organs and cell types: affinity moiety targeting, which conjugates nanoparticles to antibodies or similar molecules that bind to known surface markers on cells; and physi…
View article: Effective Prevention of Arterial Thrombosis with Albumin-Thrombin Inhibitor Conjugates
Effective Prevention of Arterial Thrombosis with Albumin-Thrombin Inhibitor Conjugates Open
Thromboprophylaxis is indicated in patients at an elevated risk of developing thrombotic disorders, typically using direct oral anticoagulants or low-molecular-weight heparins. We postulated that transient thromboprophylaxis (days-weeks) c…
View article: Physicochemical Targeting of Lipid Nanoparticles to the Lungs Induces Clotting: Mechanisms and Solutions
Physicochemical Targeting of Lipid Nanoparticles to the Lungs Induces Clotting: Mechanisms and Solutions Open
Lipid nanoparticles (LNPs) have become the dominant drug delivery technology in industry, holding the promise to deliver RNA to up- or down-regulate any protein of interest. LNPs have been targeted to specific cell types or organs by physi…
View article: Targeted Nanocarriers Co-Opting Pulmonary Intravascular Leukocytes for Drug Delivery to the Injured Brain
Targeted Nanocarriers Co-Opting Pulmonary Intravascular Leukocytes for Drug Delivery to the Injured Brain Open
Ex vivo-loaded white blood cells (WBC) can transfer cargo to pathological foci in the central nervous system (CNS). Here we tested affinity ligand driven in vivo loading of WBC in order to bypass the need for ex vivo W…
View article: Targeting lipid nanoparticles to the blood brain barrier to ameliorate acute ischemic stroke
Targeting lipid nanoparticles to the blood brain barrier to ameliorate acute ischemic stroke Open
After more than 100 failed drug trials for acute ischemic stroke (AIS), one of the most commonly cited reasons for the failure has been that drugs achieve very low concentrations in the at-risk penumbra. To address this problem, here we em…
View article: Meta-analysis of material properties influencing nanoparticle plasma pharmacokinetics
Meta-analysis of material properties influencing nanoparticle plasma pharmacokinetics Open
View article: Targeted drug delivery to the brain endothelium dominates over passive delivery via vascular leak in experimental intracerebral hemorrhage
Targeted drug delivery to the brain endothelium dominates over passive delivery via vascular leak in experimental intracerebral hemorrhage Open
View article: Mechanisms by Which Liposomes Improve Inhaled Drug Delivery for Alveolar Diseases
Mechanisms by Which Liposomes Improve Inhaled Drug Delivery for Alveolar Diseases Open
Nanomedicine Drug-filled lipid nanocarriers are inhaled for deposition in the alveoli, spherical sacs that are the functional unit of the lung. In article number 2200106, Jacob S. Brenner and co-workers demonstrate that inhaled liposomes a…
View article: Mechanisms by Which Liposomes Improve Inhaled Drug Delivery for Alveolar Diseases
Mechanisms by Which Liposomes Improve Inhaled Drug Delivery for Alveolar Diseases Open
Diseases of the pulmonary alveolus, such as pulmonary fibrosis, are leading causes of morbidity and mortality, but exceedingly few drugs are developed for them. A major reason for this gap is that after inhalation, drugs are quickly whiske…
View article: Nanoparticle-Induced Augmentation of Neutrophils’ Phagocytosis of Bacteria
Nanoparticle-Induced Augmentation of Neutrophils’ Phagocytosis of Bacteria Open
Despite the power of antibiotics, bacterial infections remain a major killer, due to antibiotic resistance and hosts with dysregulated immune systems. We and others have been developing drug-loaded nanoparticles that home to the sites of i…
View article: Nanoparticle-induced augmentation of neutrophils’ phagocytosis of bacteria
Nanoparticle-induced augmentation of neutrophils’ phagocytosis of bacteria Open
Despite the power of antibiotics, bacterial infections remain a major killer, due to antibiotic resistance and hosts with dysregulated immune systems. We and others have been developing drug-loaded nanoparticles that home to the sites of i…
View article: Dual Affinity to RBCs and Target Cells (DART) Enhances Both Organ- and Cell Type-Targeting of Intravascular Nanocarriers
Dual Affinity to RBCs and Target Cells (DART) Enhances Both Organ- and Cell Type-Targeting of Intravascular Nanocarriers Open
A long-standing goal of nanomedicine is to improve a drug's benefit by loading it into a nanocarrier that homes solely to a specific target cell and organ. Unfortunately, nanocarriers usually end up with only a small percentage of the inje…
View article: Targeted nanocarriers coopting pulmonary leukocytes for drug delivery to the injured brain
Targeted nanocarriers coopting pulmonary leukocytes for drug delivery to the injured brain Open
Selective drug delivery to injured regions of the brain is an elusive, but biomedically important, goal. It is tempting to co-opt migrating white blood cells (WBC) to carry drugs to the injured brain, using natural WBC tropism. Current app…
View article: Added to pre-existing inflammation, mRNA-lipid nanoparticles induce inflammation exacerbation (IE)
Added to pre-existing inflammation, mRNA-lipid nanoparticles induce inflammation exacerbation (IE) Open