A5025184523- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Advanced biosensing and bioanalysis techniques
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Nanowire Synthesis and Applications
- Nanoplatforms for cancer theranostics
- MicroRNA in disease regulation
- Pregnancy and preeclampsia studies
- Extracellular vesicles in disease
- 3D Printing in Biomedical Research
- Virology and Viral Diseases
- Viral Infectious Diseases and Gene Expression in Insects
- Mosquito-borne diseases and control
- COVID-19 epidemiological studies
- Circular RNAs in diseases
- RNA Research and Splicing
- Nanoparticle-Based Drug Delivery
- Electrospun Nanofibers in Biomedical Applications
- Drug Transport and Resistance Mechanisms
- Tissue Engineering and Regenerative Medicine
- Blood Coagulation and Thrombosis Mechanisms
- Innovative Microfluidic and Catalytic Techniques Innovation
- Neuroinflammation and Neurodegeneration Mechanisms
University of Pennsylvania
2021-2025
California University of Pennsylvania
2025
University of Oklahoma
2019-2022
Viral engineered chimeric antigen receptor (CAR) T cell therapies are potent, targeted cancer immunotherapies, but their permanent CAR expression can lead to severe adverse effects. Nonviral messenger RNA (mRNA) cells being explored overcome these drawbacks, electroporation, the most common transfection method, is limited by cytotoxicity. As a potentially safer nonviral delivery strategy, here, sequential libraries of ionizable lipid nanoparticle (LNP) formulations with varied excipient...
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...
Abstract With six therapies approved by the Food and Drug Association, chimeric antigen receptor (CAR) T cells have reshaped cancer immunotherapy. However, these rely on ex vivo viral transduction to induce permanent CAR expression in cells, which contributes high production costs long‐term side effects. Thus, this work aims develop an cell engineering platform streamline while using mRNA transient, tunable expression. Specifically, ionizable lipid nanoparticle (LNP) is utilized as platforms...
The programmed cell death protein 1 (PD-1) signaling pathway is a major source of dampened T activity in the tumor microenvironment. While clinical approaches to inhibiting PD-1 using antibody blockade have been broadly successful, these lead widespread suppression, increasing risk autoimmune reactions. This study reports development an ionizable lipid nanoparticle (LNP) platform for simultaneous therapeutic gene expression and RNA interference (RNAi)-mediated transient knockdown cells. In...
Abstract Lipid nanoparticles for delivering mRNA therapeutics hold immense promise the treatment of a wide range lung-associated diseases. However, lack effective methodologies capable identifying pulmonary delivery profile chemically distinct lipid libraries poses significant obstacle to advancement therapeutics. Here we report implementation barcoded high-throughput screening system as means identify lung-targeting efficacy cationic, degradable lipid-like materials. We combinatorially...
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...
Abstract A safe and effective vaccine with long-term protection against SARS-CoV-2 variants of concern (VOCs) is a global health priority. Here, we develop lipid nanoparticles (LNPs) to provide delivery plasmid DNA (pDNA) show VOCs in female small animal models. Using library LNPs encapsulating unique barcoded (b-DNA), screen for b-DNA after intramuscular administration. The top-performing are further tested their capacity pDNA uptake antigen-presenting cells vitro. lead LNP used encapsulate...
The promise of therapeutic nucleic acids has long been tempered by difficulty in overcoming biological barriers to their delivery. past two decades have seen the development ionizable lipid nanoparticles as a vehicle for acid delivery and translation clinic.
Multiple myeloma (MM), a hematologic malignancy that preferentially colonizes the bone marrow, remains incurable with survival rate of 3 to 6 mo for those advanced disease despite great efforts develop effective therapies. Thus, there is an urgent clinical need innovative and more MM therapeutics. Insights suggest endothelial cells within marrow microenvironment play critical role. Specifically, cyclophilin A (CyPA), homing factor secreted by (BMECs), homing, progression, survival,...
Lipid nanoparticles (LNPs) have emerged as a viable, clinically-validated platform for the delivery of mRNA therapeutics. LNPs been utilized systems applications including vaccines, gene therapy, and cancer immunotherapy. However, LNPs, which are typically composed ionizable lipids, cholesterol, helper lipid-anchored polyethylene glycol, often traffic to liver limits therapeutic potential platform. Several approaches proposed resolve this tropism such post-synthesis surface modification or...
Introduction: Immunotherapy has revolutionized cancer treatment by harnessing the immune system to enhance antitumor responses while minimizing off-target effects. Among promising cancer-specific therapies, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) attracted significant attention. Methods: Here, we developed an ionizable lipid nanoparticle (LNP) platform deliver TRAIL mRNA (LNP-TRAIL) directly microenvironment (TME) induce cell death. Our LNP-TRAIL was formulated via...
Monogenic blood diseases are among the most common genetic disorders worldwide. These result in significant pediatric and adult morbidity, some can death prior to birth. Novel ex vivo hematopoietic stem cell (HSC) gene editing therapies hold tremendous promise alter therapeutic landscape but not without potential limitations. In offer a potentially safer more accessible treatment for these hindered by lack of delivery vectors targeting HSCs, which reside difficult-to-access bone marrow...
Three-dimensional (3D) bioprinting holds the promise to fabricate tissue and organ substitutes for regenerative medicine. However, lack of bioactive inks support functional living constructs is one main limitations hindering progress this technology. In study, a biofunctional human-based nanocomposite bioink (HUink) composed platelet lysate hydrogels reinforced by cellulose nanocrystals reported. When combined with suspended technologies, HUink allows biofabrication 3D freeform high...
During healthy pregnancy, the placenta develops to allow for exchange of nutrients and oxygen between mother fetus. However, placental dysregulation can lead several pregnancy disorders, such as preeclampsia fetal growth restriction. Recently, lipid nanoparticle (LNP)-mediated delivery messenger RNA (mRNA) has been explored a promising approach treat these disorders. Here, iterative libraries LNPs with varied excipient molar ratios are screened in vitro enhanced mRNA cells minimal...
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....
Immune modulation through the intracellular delivery of nucleoside-modified mRNA to immune cells is an attractive approach for in vivo immunoengineering, with applications infectious disease, cancer immunotherapy, and beyond. Lipid nanoparticles (LNPs) have come fore as a promising nucleic acid platform, but LNP design criteria remain poorly defined, making rate-limiting step discovery screening process. In this study, we employed high-throughput based on molecular barcoding investigate...
Cell-based therapies for autoimmune diseases have gained significant traction, with several approaches centered around the regulatory T (Treg) cell─a well-known immunosuppressive cell characterized by its expression of transcription factor Foxp3. Unfortunately, due to low numbers Treg cells available in circulation, harvesting and culturing remains a challenge. It has been reported that engineering Foxp3 CD4+ can result Treg-like phenotype; however, current methods inefficient these cells....
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,...
It is well established that the physicochemical properties of lipid nanoparticles (LNPs) can govern their interactions with various biological barriers. One property hypothesized to influence nanoparticle-cell elasticity. Here, we formulate LNPs naturally occurring cholesterol analogs tune LNP elasticity and study its role on mRNA delivery placenta. was measured via atomic force microscopy where these exhibited Young's moduli ranging from 71.0 ± 26.2 411.4 145.7 kPa. In vitro screening in...