A5046388197- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Antimicrobial Peptides and Activities
- Virology and Viral Diseases
- Respiratory viral infections research
- Peptidase Inhibition and Analysis
- Glycosylation and Glycoproteins Research
- Lipid Membrane Structure and Behavior
- SARS-CoV-2 and COVID-19 Research
- Click Chemistry and Applications
- Antimicrobial agents and applications
- Nanoparticle-Based Drug Delivery
- MicroRNA in disease regulation
- Conducting polymers and applications
- Immunotherapy and Immune Responses
- Influenza Virus Research Studies
- Advanced Polymer Synthesis and Characterization
- HER2/EGFR in Cancer Research
- Virus-based gene therapy research
- Bacteriophages and microbial interactions
- Fuel Cells and Related Materials
- Fullerene Chemistry and Applications
- Galectins and Cancer Biology
Cornell University
2016-2025
Smith Institute
2024
Ithaca College
2018-2021
Massachusetts Institute of Technology
2010-2014
California Institute of Technology
2006-2010
Wythenshawe Hospital
2006
New York University
2002-2003
PEGylated gold nanoparticles are decorated with various amounts of human transferrin (Tf) to give a series Tf-targeted particles near-constant size and electrokinetic potential. The effects Tf content on nanoparticle tumor targeting were investigated in mice bearing s.c. Neuro2A tumors. Quantitative biodistributions the 24 h after i.v. tail-vein injections show that accumulations tumors other organs independent Tf. However, localizations within particular organ influenced by content. In...
Significance The safe, selective, and efficient delivery of siRNA is a key challenge to the broad application therapeutics in humans. Motivated by structure lipoproteins, we developed lipopeptide nanomaterials for delivery. In vivo mice, siRNA–lipopeptide particles provide most potent hepatocytes (ED 50 ∼ 0.002 mg/kg FVII silencing), with highest selectivity over nontarget cell types (orders magnitude), yet reported. These materials also show efficacy nonhuman primates.
Biological systems have long recognized the importance of macromolecular diversity and evolved efficient processes for rapid synthesis sequence-defined biopolymers. However, achieving sequence control via synthetic methods has proven to be a difficult challenge. Herein we describe efforts circumvent this difficulty use orthogonal allyl acrylamide building blocks liquid-phase fluorous support de novo design sequence-specific polymers. We demonstrate proof-of-concept characterization two...
Halting transmission The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein binds to host cells and initiates membrane fusion cell infection. This stage in the virus life history is currently a target for drug inhibition. De Vries et al. designed highly stable lipoprotein inhibitors complementary conserved repeat C terminus of S that integrate into membranes inhibit conformational changes necessary fusion. authors tested performance lipoproteins as...
IT-101, a cyclodextrin polymer-based nanoparticle containing camptothecin, is in clinical development for the treatment of cancer. Multiorgan pharmacokinetics and accumulation tumor tissue IT-101 investigated by using PET. modified through attachment 1,4,7,10-tetraazacyclododecane-1,4,7-Tris-acetic acid ligand to bind 64 Cu 2+ . This modification does not affect particle size minimally affects surface charge resulting nanoparticles. PET data from Cu-labeled are used quantify vivo...
Nanoparticle-mediated siRNA delivery is a complex process that requires transport across numerous extracellular and intracellular barriers. As such, the development of nanoparticles for efficient would benefit from an understanding how parameters associated with these barriers relate to physicochemical properties nanoparticles. Here, we use multiparametric approach evaluation lipid (LNPs) identify relationships between structure, biological function, activity. Our results indicate multiple...
Degradable, cationic poly(β-amino ester)s (PBAEs) with alkyl side chains are developed for non-viral gene delivery. Nanoparticles formed from these PBAE terpolymers exhibit significantly enhanced DNA transfection potency and resistance to aggregation. These hydrophobic terpolymers, but not PBAEs lacking chains, support interaction PEG-lipid conjugates, facilitating their functionalization shielding targeting moieties accelerating the in vivo translation of materials. As a service our authors...
Abstract We have assessed antiviral activity and induction of protective immunity fusion-inhibitory lipopeptides derived from the C-terminal heptad-repeat domain SARS-CoV-2 spike glycoprotein in transgenic mice expressing human ACE2 (K18-hACE2). The block infection cell lines lung-derived organotypic cultures. Intranasal administration allows maintenance homeostatic transcriptomic immune profile lungs, prevents body-weight loss, decreases viral load shedding, protects death caused by...
To date, scalability limitations have hindered the exploration and application of sequence-defined polymers in areas such as synthetic plastics, fibers, rubbers, coatings, composites. Additionally, impact sequence on properties cross-linked networks remains largely unknown. address need for methods to generate materials gram quantities, we developed a strategy involving inexpensive readily functional vanillin-based monomers assemble polyurethane oligomers via sequential reductive amination...
Despite the promise of RNA interference (RNAi) therapeutics, progress toward clinic has been slowed by difficulty delivering short interfering (siRNA) into cellular targets within body. Nearly all siRNA delivery vehicles developed to date employ a single cationic or ionizable material. In order increase material space available for development this study examined possibility using binary combinations lipid-like materials synergistically achieve gene silencing. Interestingly, it was found...
The assembly, stability, and timely disassembly of short interfering RNA (siRNA) nanocomplexes have the potential to affect efficiency siRNA delivery gene silencing. As such, design new probes that can measure these properties without significantly perturbing or their environment may facilitate study further development nanocomplexes. Herein, we Förster resonance energy transfer (FRET)-labeled track in different environments. probe is composed two identical siRNAs, each labeled with a...
New lipid-like nanomaterials are developed to simultaneously regulate expression of multiple genes. Self-assembled nanoparticles capable efficiently encapsulating pDNA and siRNA. These shown induce simultaneous gene silencing both in vitro vivo. As a service our authors readers, this journal provides supporting information supplied by the authors. Such materials peer reviewed may be re-organized for online delivery, but not copy-edited or typeset. Technical support issues arising from (other...
Abstract Antibiotic discovery has experienced a severe slowdown in terms of new candidates. In vitro screening methods using phospholipids to model the bacterial membrane provide route identify molecules that specifically disrupt membranes causing cell death. Thanks electrically insulating properties major component membrane, phospholipids, electronic devices are highly suitable transducers disruption. The organic electrochemical transistor (OECT) is sensitive ion‐to‐electron converter....
Protein-based therapeutics comprise a rapidly growing subset of pharmaceuticals, but enabling their delivery into cells for intracellular applications has been longstanding challenge. To overcome the barrier, we explored reversible, bioconjugation-based approach to modify surface charge protein cargos with an anionic "cloak" facilitate electrostatic complexation and lipid nanoparticle (LNP) formulations. We demonstrate that conjugation lysine-reactive sulfonated compounds can allow various...
ABSTRACT Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes death among young children worldwide despite availability an effective measles vaccine. MV infects its target cells by coordinated action hemagglutinin (H) fusion (F) envelope glycoproteins; upon receptor engagement H, prefusion F undergoes a structural transition, extending inserting into cell membrane then refolding postfusion structure that fuses viral membranes. By interfering with this...
In response to the urgent need for new antibiotic development strategies, antimicrobial peptides (AMPs) and other synthetic polymers are being actively investigated as promising alternatives traditional antibiotics. Although most AMPs display lytic activity against several types of bacteria, they have poor toxicology profiles susceptible proteolysis in vivo. While many variants been created mimic by tuning hydrophobic cationic ratio side-chain groups, few decoupled effects charge from...
Antibody–drug conjugates utilize the antigen specificity of antibodies and potency chemotherapeutic antibiotic drugs for targeted therapy. However, as cancers bacteria evolve to resist action drugs, innovative controlled release methods must be engineered deliver multidrug cocktails. In this work, we engineer lipoate-acid ligase A (LplA) acceptor peptide (LAP) tags into constant heavy light chain a humanized Her2 antibody, trastuzumab. These LAP tags, along with glutamine 295 (Q295) residue...
Site-specific modification of native antibodies has proven advantageous, as it enhances the properties antibody-based bioconjugates without need to manipulate genetic code. However, antibody is typically limited strategies that introduce a single functional handle. In this work, we addressed limitation by designing heterobifunctional substrates for microbial transglutaminase (MTG) contain both azide and methyltetrazine “click” handles. Structure-conjugation relationships these were evaluated...