A5010666650- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Advanced Drug Delivery Systems
- Immunotherapy and Immune Responses
- Nanoparticle-Based Drug Delivery
- Virus-based gene therapy research
- MicroRNA in disease regulation
- Infant Nutrition and Health
- Drug Transport and Resistance Mechanisms
- Drug Solubulity and Delivery Systems
- Extracellular vesicles in disease
- Pregnancy and preeclampsia studies
- Lipid Membrane Structure and Behavior
- Graphene and Nanomaterials Applications
- Gastrointestinal motility and disorders
- Lymphoma Diagnosis and Treatment
- 3D Printing in Biomedical Research
- Biochemical Analysis and Sensing Techniques
- Neonatal Respiratory Health Research
- Clinical Nutrition and Gastroenterology
- Advancements in Transdermal Drug Delivery
- Digestive system and related health
- CAR-T cell therapy research
- Barrier Structure and Function Studies
- Reproductive System and Pregnancy
Carnegie Mellon University
2016-2025
Massachusetts Institute of Technology
2009-2014
Weatherford College
2014
Alnylam Pharmaceuticals (United States)
2010
Koch Institute for Integrative Cancer Research At MIT
2010
Allen Institute
2010
University of California, Santa Barbara
2004-2008
Significant effort has been applied to discover and develop vehicles which can guide small interfering RNAs (siRNA) through the many barriers guarding interior of target cells. While studies have demonstrated potential gene silencing in vivo, improvements delivery efficacy are required fulfill broadest RNA interference therapeutics. Through combinatorial synthesis screening a different class materials, formulation identified that enables siRNA-directed liver mice at doses below 0.01 mg/kg....
The discovery of potent new materials for in vivo delivery nucleic acids depends upon successful formulation the active molecules into a dosage form suitable physiological environment. Because inefficiencies current methods, are usually first evaluated vitro efficacy as simple ionic complexes with (lipoplexes). predictive value such assays, however, has never been systematically studied. Here, time, by developing microfluidic method that allowed rapid preparation high-quality...
Although mRNA and siRNA have significant therapeutic potential, their simultaneous delivery has not been previously explored. To facilitate the treatment of diseases associated with aberrant gene upregulation downregulation, we sought to co-formulate in a single lipidoid nanoparticle (LNP) formulation. We accommodated distinct molecular characteristics formulation consisting an ionizable biodegradable amine-containing lipidoid, cholesterol, DSPC, DOPE, PEG-lipid. Surprisingly, co-formulation...
Abstract: The broadest clinical application of siRNA therapeutics will be facilitated by drug-loaded delivery systems that maintain stability and potency for long times under ambient conditions. In the present study, we seek to better understand effect storage conditions on lipidoid nanoparticles (LNPs), which have been previously shown our group others potently deliver RNA various cell organ targets both in vitro vivo. Specifically, this study evaluates influence pH, temperature,...
Abstract The potential of mRNA therapeutics will be realized only once safe and effective delivery systems are established. Unfortunately, vehicle development is stymied by an inadequate understanding how the molecular properties a confer efficacy. Here, small library lipidoid materials used to elucidate structure–function relationships identify previously unappreciated parameter—lipid nanoparticle surface ionization—that correlates with two most potent library, 306O 10 i10 , induce...
The broad clinical application of mRNA therapeutics has been hampered by a lack delivery vehicles that induce protein expression in extrahepatic organs and tissues. Recently, it was shown to the spleen or lungs is possible upon addition charged lipid standard four-component nanoparticle formulation. This approach, while effective, further complicates an already complex drug formulation potential slow regulatory approval adversely impact manufacturing processes. We were thus motivated...
Systemic messenger RNA (mRNA) delivery to organs outside the liver, spleen, and lungs remains challenging. To overcome this issue, we hypothesized that altering nanoparticle chemistry administration routes may enable mRNA-induced protein expression of reticuloendothelial system. Here, describe a strategy for delivering mRNA potently specifically pancreas using lipid nanoparticles. Our results show nanoparticles containing cationic helper lipids by intraperitoneal produces robust specific in...
Abstract Lipid nanoparticles (LNPs) have emerged as the dominant platform for RNA delivery, based on their success in COVID-19 vaccines and late-stage clinical studies other indications. However, we others shown that LNPs induce severe inflammation, massively aggravate pre-existing inflammation. Here, using structure-function screening of lipids analyses signaling pathways, elucidate mechanisms LNP-associated inflammation demonstrate solutions. We show LNPs’ hallmark feature, endosomal...
Treating pregnancy-related disorders is exceptionally challenging because the threat of maternal and/or fetal toxicity discourages use existing medications and hinders new drug development. One potential solution lipid nanoparticle (LNP) RNA therapies, given their proven efficacy, tolerability, lack accumulation. Here, we describe LNPs for efficacious mRNA delivery to organs in pregnant mice via several routes administration. In placenta, our lead LNP transfected trophoblasts, endothelial...
Analogous to an assembly line, we employed a modular design for the high-throughput study of 1,536 structurally distinct nanoparticles with cationic cores and variable shells. This enabled elucidation complexation, internalization, delivery trends that could only be learned through evaluation large library. Using robotic automation, epoxide-functionalized block polymers were combinatorially cross-linked diverse library amines, followed by measurement molecular weight, diameter, RNA cellular...
In this article, we review critical aspects in the area of drug delivery. Specifically, delivery siRNA, remote-controlled delivery, noninvasive and nanotechnology are reviewed.
The targeted delivery of therapeutics to tumors remains an important challenge in cancer nanomedicine. Attaching nanoparticles cells that have tumoritropic migratory properties is a promising modality address this challenge. Here we describe technique create nanoparticulate cellular patches remain attached the membrane for up 2 days. NeutrAvidin-coated were anchored on possessing biotinylated plasma membrane. Human bone marrow derived mesenchymal stem with retained their inherent as shown...
A significant challenge in the development of clinically viable siRNA delivery systems is a lack vitro–in vivo translatability: many vehicles that are initially promising cell culture do not retain efficacy animals. Despite its importance, little information exists on predictive nature vitro methodologies, most likely due to cost and time associated with generating data sets. Recently, high-throughput techniques have been developed allowed examination hundreds lipid nanoparticle formulations...
Oral delivery, a patient-friendly means of drug is preferred for local administration intestinal therapeutics. Lipidoid nanoparticles, which have been previously shown to deliver siRNA epithelial cells, potential treat disease. It unknown, however, whether the oral delivery these particles possible. To better understand fate lipid nanoparticles in gastrointestinal (GI) tract, we studied under deconstructed stomach and conditions vitro. Lipid remained potent stable following exposure...
The clinical translation of messengerRNA (mRNA) drugs has been slowed by a shortage delivery vehicles that potently and safely shuttle mRNA into target cells. Here, we describe the properties particularly potent branched-tail lipid nanoparticle delivers to >80% three major liver cell types. We characterize spatially, temporally, as function injection type. Following intravenous delivery, our induced greater protein expression than two benchmark lipids, C12-200 DLin-MC3-DMA, at an dose 0.5...