A5052880510- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Lipid Membrane Structure and Behavior
- Pancreatic function and diabetes
- Virus-based gene therapy research
- Nanoparticle-Based Drug Delivery
- Extracellular vesicles in disease
- Microfluidic and Bio-sensing Technologies
- Nanoplatforms for cancer theranostics
- Metabolism, Diabetes, and Cancer
- Diabetes Treatment and Management
- Nanopore and Nanochannel Transport Studies
- Advanced Drug Delivery Systems
- Viral gastroenteritis research and epidemiology
- Fluid Dynamics and Turbulent Flows
- Animal Virus Infections Studies
- Hepatocellular Carcinoma Treatment and Prognosis
- Innovative Microfluidic and Catalytic Techniques Innovation
- Lattice Boltzmann Simulation Studies
- Heat Transfer Mechanisms
- Molecular Communication and Nanonetworks
- Gold and Silver Nanoparticles Synthesis and Applications
- Microtubule and mitosis dynamics
- Viral Infections and Immunology Research
- Immunotherapy and Immune Responses
Johns Hopkins University
2017-2024
Johns Hopkins Medicine
2017-2024
Massachusetts Institute of Technology
2023-2024
University of Baltimore
2018
Abstract Lipid nanoparticles (LNPs) are effective vehicles to deliver mRNA vaccines and therapeutics. It has been challenging assess packaging characteristics in LNPs, including payload distribution capacity, which critical understanding structure-property-function relationships for further carrier development. Here, we report a method based on the multi-laser cylindrical illumination confocal spectroscopy (CICS) technique examine lipid contents LNP formulations at single-nanoparticle level....
Abstract Lipid nanoparticles hold great potential as an effective non-viral vector for nucleic acid-based gene therapy. Plasmid DNA delivery can result in extended transgene expression compared to mRNA-based technologies, yet there is a lack of systematic investigation into lipid nanoparticle compositions plasmid delivery. Here, we report multi-step screening platform identify optimized liver-targeted expression. To achieve this, analyze the role different helper lipids and component ratios...
Nanoparticle-based RNA delivery has shown great progress in recent years with the approval of two mRNA vaccines for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and a liver-targeted siRNA therapy. Here, we discuss preclinical clinical advancement new generations therapies along multiple axes. Improvements cargo design such as circularization data-driven untranslated region optimization can drive better expression. New materials discovery research driven improved to...
Flash Nanocomplexation (FNC) as a scalable manufacturing method to facilitate successful clinical translation of protein therapeutics.
Nanoparticles designed as messenger RNA (mRNA) carriers to deliver gene medicine have shown great potential change the way lung disease states are managed. Controlling their delivery and transgene expression in a specific population of cells remains challenge. Here, we developed series nanoparticles with polyethylene glycol (PEG) corona prepared by condensing mRNA PEG-grafted-polyethyleneimine (PEI-g-PEG) different PEG terminal functional groups grafting ratios. PEGylated (PEG ratio was...
Polyelectrolyte complex (PEC) nanoparticles assembled from plasmid DNA (pDNA) and polycations such as linear polyethylenimine (lPEI) represent a major nonviral delivery vehicle for gene therapy tested thus far. Efforts to control the size, shape, surface properties of pDNA/polycation have been primarily focused on fine-tuning molecular structures polycationic carriers assembly conditions medium polarity, pH, temperature. However, reproducible production these hinges ability kinetics, given...
Lipid nanoparticles (LNP) have emerged as pivotal delivery vehicles for RNA therapeutics. Previous research and development usually assumed that LNPs are homogeneous in population, loading density, composition. Such perspectives difficult to examine due the lack of suitable tools characterize these physicochemical properties at single-nanoparticle level. Here, we report an integrated spectroscopy-chromatography approach a generalizable strategy dissect complexities multicomponent LNP...
Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related mortality in world. Over past two decades, there has been minimal improvement therapies as well clinical outcomes for patients with Barcelona Clinic Liver Cancer (BCLC)-B. These are treated local interventions, including transarterial chemoembolization. Current methodologies only allow sustained intratumoral release measured hours. Methodologies to drug cargo over days weeks acutely needed. We hypothesize...
The transfection efficiency and stability of the delivery vehicles plasmid DNA (pDNA) are critical metrics to ensure high-quality high-yield production viral vectors. We previously identified that optimal size pDNA/poly(ethylenimine) (PEI) particles is 400–500 nm developed a bottom-up assembly method construct stable 400-nm pDNA/PEI benchmarked their in producing lentiviral vectors (LVVs). Here, we report scale-up protocols for such particles. Using two-inlet confined impinging jet (CIJ)...
Size-dependent phagocytosis is a well-characterized phenomenon in monocytes and macrophages. However, this size effect for preferential gene delivery to these important cell targets has not been fully exploited because commonly adopted stabilization methods electrostatically complexed nucleic acid nanoparticles, such as PEGylation charge repulsion, typically arrest the vehicle below 200 nm. Here, we bridge technical gap scalable synthesis of larger submicron vehicles by electrostatic...
Lipid nanoparticles (LNPs) have great potential to enable inhaled delivery of mRNA treat pulmonary diseases. However, this has been limited by the challenge nebulizing LNPs. Nebulization LNPs can cause aggregate and release encapsulated mRNA, limiting their efficacy. To overcome challenge, are developed whereby PEG-lipid is fully replaced with a zwitterionic polymer (ZIP)-lipid conjugate greatly enhance nebulizer stability. formulated ZIP-lipids (ZIP-LNPs) were stable nebulization across...
Polyelectrolyte complex particles assembled from plasmid DNA (pDNA) and poly(ethylenimine) (PEI) have been widely used to produce lentiviral vectors (LVVs) for gene therapy. The current batch-mode preparation pDNA/PEI presents limited reproducibility in large-scale LVV manufacturing processes, leading challenges tightly controlling particle stability, transfection outcomes, production yield. Here we identified the size of as a key determinant high efficiency with an optimal 400–500 nm, due...
Due to their ability provide efficient mixing at small scales, confined impinging jet mixers (CIJMs) are employed widely in nanoparticle assembly processes such as flash nanoprecipitation and nanocomplexation, which require rapid mixing. In this device, two jets from opposite directions impinge directly on each other forming a thin shear layer that breaks down rapidly into flow structures. This enables effective of the species transported by drastically reducing diffusion distance. present...
Plasmid DNA (pDNA) nanoparticles synthesized by complexation with linear polyethylenimine (lPEI) are one of the most effective non-viral gene delivery vehicles. However, lack scalable and reproducible production methods high toxicity have hindered their clinical translation. Previously, we developed a flash nanocomplexation (FNC) technique to formulate pDNA/lPEI using continuous flow process. Here, report tangential filtration (TFF)-based purification method reduce uncomplexed lPEI...
Abstract Treatment of cancers in the lung remains a critical challenge clinic for which gene therapy could offer valuable options. We describe an effective approach through systemic injection engineered polymer/DNA nanoparticles that mediate tumor-specific expression therapeutic gene, under control cancer-selective progression elevated 3 ( PEG-3 ) promoter, to treat tumors lungs diseased mice. A clinically tested, untargeted, polyethylenimine carrier was selected aid rapid transition...