A5074948959- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Lipid Membrane Structure and Behavior
- CAR-T cell therapy research
- Virus-based gene therapy research
- Nanoparticle-Based Drug Delivery
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Pregnancy and preeclampsia studies
- CRISPR and Genetic Engineering
- Photochromic and Fluorescence Chemistry
- Immune Cell Function and Interaction
- Protein Interaction Studies and Fluorescence Analysis
- Organoboron and organosilicon chemistry
- Blood Coagulation and Thrombosis Mechanisms
- Nanowire Synthesis and Applications
- Viral Infections and Immunology Research
- Bacteriophages and microbial interactions
- Bone and Joint Diseases
- Photoreceptor and optogenetics research
- Chemical Reactions and Mechanisms
- Analytical chemistry methods development
- RNA and protein synthesis mechanisms
- Ionic liquids properties and applications
University of Pennsylvania
2022-2025
California University of Pennsylvania
2024-2025
University of Wisconsin–Madison
2021-2023
Madison Group (United States)
2021
William & Mary
2014-2017
Williams (United States)
2014-2017
Colonial Williamsburg Foundation
2014
The development of lipid nanoparticle (LNP) formulations for targeting the bone microenvironment holds significant potential nucleic acid therapeutic applications including regeneration, cancer, and hematopoietic stem cell therapies. However, delivery to remains a challenge due several biological barriers, such as low blood flow in bone, blood–bone marrow affinity between drugs minerals, which leads unfavorable dosages microenvironment. Here, we construct series bisphosphonate (BP)...
Ionizable lipid nanoparticles (LNPs) are the most clinically advanced nonviral platform for mRNA delivery. While they have been explored applications including vaccines and gene editing, LNPs not investigated placental insufficiency during pregnancy. Placental is caused by inadequate blood flow in placenta, which results increased maternal pressure restricted fetal growth. Therefore, improving vasodilation placenta can benefit both health. Here, we engineered ionizable delivery to with...
Lipid nanoparticles (LNPs) are a potent delivery technology that have made it possible for the recent clinical breakthroughs in mRNA therapeutics and vaccines. A key challenge to broader implementation of vaccines is development produce precisely defined LNP formulations, with throughput can scale from discovery commercial manufacturing meet stringent standards pharmaceutical industry. To address these challenges, we developed microfluidic chip incorporates 1×, 10×, or 256× LNP-generating...
Abstract Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable clinical success in the treatment of hematological malignancies. However, producing these bespoke cancer‐killing cells is a complicated ex vivo process involving leukapheresis, artificial activation, and CAR construct introduction. The activation step requires engagement CD3/TCR CD28 vital for transfection differentiation. Though antigen‐presenting (APCs) facilitate vivo, relies on antibodies against CD3...
Lipid nanoparticle (LNP)-mediated nucleic acid therapies, including mRNA protein replacement and gene editing hold great potential in treating neurological disorders neurodegeneration, brain cancer, stroke. However, delivering LNPs across the blood-brain barrier (BBB) after systemic administration remains underexplored. In this work, we engineered a high-throughput screening transwell platform for BBB (HTS-BBB), specifically optimized LNPs. Unlike most assays, which only assess transport an...
RNA-based therapeutics have gained traction for the prevention and treatment of a variety diseases. However, their fragility immunogenicity necessitate drug carrier. Lipid nanoparticles (LNPs) emerged as predominant delivery vehicle RNA therapeutics. An important component LNPs is ionizable lipid (IL), which protonated in acidic environment endosome, prompting cargo release into cytosol. Currently, there growing evidence that structure IL tails significantly impacts efficacy LNP-mediated...
Lipid nanoparticles (LNPs) play a crucial role in delivering messenger RNA (mRNA) therapeutics for clinical applications, including COVID-19 mRNA vaccines. While can be chemically modified to become immune-silent and increase protein expression, LNPs still trigger innate immune responses cause inflammation-related adverse effects. Inflammation turn suppress translation reduce the therapeutic effect. Dexamethasone (Dex) is widely used anti-inflammatory corticosteroid medication that...
Mutated RAS proteins are potent oncogenic drivers and have long been considered "undruggable". While RAS-targeting therapies recently shown promise, there remains a clinical need for inhibitors with more diverse targets. Small represent potential new therapeutic option, including K27, designed ankyrin repeat protein (DARPin) engineered to inhibit RAS. However, K27 functions intracellularly is incapable of entering the cytosol on its own, currently limiting utility. To overcome this barrier,...
Abstract Chimeric antigen receptor (CAR) monocyte and macrophage therapies are promising solid tumor immunotherapies that can overcome the challenges facing conventional CAR T cell therapy. mRNA lipid nanoparticles (mRNA‐LNPs) offer a viable platform for in situ engineering of monocytes with transient tunable expression to reduce off‐tumor toxicity streamline manufacturing. However, identifying LNPs tropism intracellular delivery potency is difficult using traditional screening techniques....
Systemic delivery of large nucleic acids, such as mRNA, to the brain remains challenging in part due blood-brain barrier (BBB) and tendency vehicles accumulate liver. Here, we design a peptide-functionalized lipid nanoparticle (LNP) platform for targeted mRNA brain. We utilize click chemistry functionalize LNPs with peptides that target receptors overexpressed on endothelial cells neurons, namely RVG29, T7, AP2, mApoE peptides. evaluate effect LNP targeting neuronal cell transfection vitro,...
Chimeric antigen receptor (CAR) cell therapy represents a hallmark in cancer immunotherapy, with significant clinical results the treatment of hematological tumors. However, current approved methods to engineer T cells express CAR use viral vectors, which are integrative and have been associated severe adverse effects due constitutive expression CAR. In this context, non-viral vectors such as ionizable lipid nanoparticles (LNPs) arise an alternative transient CAR.Here, we formulated...
Lipid nanoparticles (LNPs) are the most advanced delivery system currently available for RNA therapeutics. Their development has accelerated rapidly since success of Patisiran, first siRNA-LNP therapeutic, and SARS-CoV-2 mRNA vaccines that emerged during COVID-19 pandemic. Designing LNPs with specific targeting, high potency, minimal side effects is crucial their successful clinical use. However, our understanding how composition mixing methods influence structure, biophysical properties,...
Lipid nanoparticles (LNPs) have attracted widespread attention recently with the successful development of COVID-19 mRNA vaccines by Moderna and Pfizer/BioNTech. These demonstrated efficacy mRNA-LNP therapeutics opened door for future clinical applications. In systems, LNPs serve as delivery platforms that protect cargo from degradation nucleases mediate their intracellular delivery. The are typically composed four components: an ionizable lipid, a phospholipid, cholesterol, lipid-anchored...
In the past 10 years, CRISPR-Cas9 has revolutionized gene-editing field due to its modularity, simplicity, and efficacy. It been applied for creation of in vivo models, further understand human biology, toward curing genetic diseases. However, there remain significant delivery barriers application clinic, especially extrahepatic applications. this work, high-throughput molecular barcoding techniques were used alongside traditional screening methodologies simultaneously evaluate LNP...
Gemini hydrophobic ionic liquids (HILs) are synthesized and characterized. Several showcase unique properties reduced toxicity compared to traditional HILs.
Polyynes exhibit both unique photophysical properties and biological activities, necessitating efficient syntheses towards these core structures. A novel methodology for the construction of highly conjugated asymmetrical polyynes has been developed in a chemoselective fashion utilizing solid-support. The synthesis applied to prepare small library good moderate yield. Moreover, their interesting fluorescence have investigated, demonstrating ability tune through selection appropriate synthetic...