A5065413297- RNA Interference and Gene Delivery
- Platelet Disorders and Treatments
- Lipid Membrane Structure and Behavior
- SARS-CoV-2 and COVID-19 Research
- Corneal surgery and disorders
- Advanced biosensing and bioanalysis techniques
- Glaucoma and retinal disorders
- Drug Transport and Resistance Mechanisms
- Complement system in diseases
- Heparin-Induced Thrombocytopenia and Thrombosis
- Corneal Surgery and Treatments
- Systemic Lupus Erythematosus Research
- Extracellular vesicles in disease
- Blood groups and transfusion
- Angiogenesis and VEGF in Cancer
- Blood disorders and treatments
- Nanoparticle-Based Drug Delivery
- Vascular Malformations and Hemangiomas
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Lymphatic System and Diseases
- Retinal Imaging and Analysis
- MicroRNA in disease regulation
- Glycosylation and Glycoproteins Research
- Blood Coagulation and Thrombosis Mechanisms
Georgia Institute of Technology
2021-2025
The Wallace H. Coulter Department of Biomedical Engineering
2021-2025
AID Atlanta
2024
Lipid nanoparticles (LNPs) have delivered RNA to hepatocytes in patients, underscoring the potential impact of nonliver delivery. Scientists can shift LNP tropism lung by adding cationic helper lipids; however, biological response these LNPs remains understudied. To evaluate hypothesis that charged lead differential cellular responses, we quantified how 137 mRNA 19 cell types vivo. Consistent with previous studies, observed lipid-dependent tropism. After identifying and individually...
Abstract Poly(ethylene glycol) (PEG)–lipids are used in Food‐and‐Drug‐Administration‐approved lipid nanoparticle (LNP)–RNA drugs, which safe and effective. However, it is reported that PEG–lipids may also contribute to accelerated blood clearance rare cases of hypersensitivity; this highlights the utility exploring PEG–lipid alternatives. Here, shown LNPs containing poly(2‐ethyl‐2‐oxazoline) (PEOZ)–lipids can deliver messenger RNA (mRNA) multiple cell types mice inside outside liver. In...
Lipid nanoparticles (LNPs) have delivered therapeutic RNA to hepatocytes in humans. Adsorption of apolipoprotein E (ApoE) onto these clinical LNP-mRNA drugs has been shown facilitate hepatocyte entry via the low-density lipoprotein receptor (LDLR). Since ApoE-LDLR trafficking is conserved mice, non-human primates, and humans, characterizing this mechanism eased transition. Recently, LNPs mRNA non-hepatocytes mice suggesting they can target new cell types ApoE- LDLR-independent pathways. To...
To predict whether preclinical lipid nanoparticle (LNP) delivery will translate in humans, it is necessary to understand the mechanism used by LNPs enter cells conserved across species. In mice, non-human primates, and deliver RNA hepatocytes adsorbing apolipoprotein E (ApoE), which binds low-density lipoprotein receptor (LDLR). A growing number of can nonhepatocytes, suggesting that ApoE- LDLR-independent interactions could affect LNP tropism. evaluate this hypothesis, we developed a...
Elevated von Willebrand factor (VWF) levels correlate with higher risk of atherosclerosis-related arterial thrombosis (atherothrombosis). Silencing the VWF gene via small-interfering RNAs (siRNAs) could mitigate this risk. Previous studies successfully delivered siRNA to endothelium healthy, wild-type (WT) mice using lipid nanoparticles (LNPs). This study aimed investigate whether LNP-siRNA strategy achieve endothelium-specific Vwf-silencing under diseased conditions prolonged...
Transcriptomic analysis undertaken at different timepoints can shed light on mRNA-LNP in vivo delivery dynamics.
Most cancer patients diagnosed with late-stage head and neck squamous cell carcinoma are treated chemoradiotherapy, which can lead to toxicity. One potential alternative is tumor-limited conversion of a prodrug into its cytotoxic form. We reason this could be achieved by transient tumor-specific expression purine nucleoside phosphorylase (PNP), an Escherichia coli enzyme that converts fludarabine 2-fluoroadenine, potent drug. To efficiently express bacterial PNP in tumors, we evaluate 44...
An imbalance in von Willebrand factor (VWF) may either lead to bleeding (von disease, VWD) or thrombosis. Both disorders have shortcomings the currently available treatments. VWF itself could be a potential therapeutic target because of its role both and Inhibiting gene expression through allele-selective silencing with small interfering RNAs (siRNAs) personalized approach specifically inhibit mutant VWD normalize increased levels thrombotic without complete knockdown. Therefore, we...
The asialoglycoprotein receptor (ASGPR) is expressed in high density on hepatocytes. Multivalent variants of galactosyl carbohydrates bind ASGPR with affinity, enabling hepatic delivery ligand-bound cargo. Virus-like particle (VLP) conjugates a relatively high-affinity ligand were efficiently endocytosed by ASGPR-expressing cells manner strongly dependent the nature and display, best formulation using nanomolar-, but not picomolar-level, binder. Optimized particles taken up HepG2 greater...
Purpose: Scleral stiffening may protect against glaucomatous retinal ganglion cell (RGC) loss or dysfunction associated with ocular hypertension. Here, we assess the potential neuroprotective effects of two treatments designed to stiffen either entire posterior sclera only adjacent peripapillary in an experimental model glaucoma. Methods: Rat sclerae were stiffened vivo using genipin (crosslinking sclera) a regionally selective photosensitizer, methylene blue (stiffening juxtaperipapillary...
Abstract Dysfunction of the lymphatic system following injury, disease, or cancer treatment can lead to lymphedema, a debilitating condition with no cure. Advances in targeted therapy have shown promise for treating diseases where conventional therapies been ineffective and vessels recently emerged as new therapeutic target. Lipid nanoparticles (LNPs) promising strategy tissue specific delivery nucleic acids. Currently, there are approaches target LNPs endothelial cells, although it is well...