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Principal Investigator: Ekaterina Selivanovitch
Organization: CORNELL UNIVERSITY
Fiscal Year: 2024
Award: $74,284
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary /Abstract
Viruses present one of the most efficient mechanisms for intracellular cargo (i.e. viral genome)
delivery in which interactions at the virus-host cell interface dictate the delivery pathway. For
instance, enveloped viruses- those that are 'wrapped' in a lipid bilayer, deliver their genetic cargo
by first interacting with extracellular receptors, triggering a reaction cascade that results in fusion
of the virus- and host cell lipid membranes and cargo release into the cytosol. Harnessing the
efficiency of this translocation mechanism would drastically improve cellular uptake of therapeutic
and bioactive cargo, currently a major obstacle in both agricultural and pharmaceutical
communities, each with major impact on human health. The research proposed in this fellowship
aims to repurpose viral fusion machinery for delivering user-defined cargo to cells containing the
appropriate receptors. More specifically, several virus-derived proteins have been chosen
including Hemagglutinin (HA) - from Influenza, glycoprotein G (NiV-G) and fusion protein F (NiV-
F) - from Nipah virus, and Spike protein - from SARS-CoV-2. These proteins represent a small
selection of model proteins, all of which interact with different receptor types found on the cellular
surface, providing a potential handle for targeting cells that abundantly display the specific
receptors. To circumvent challenges associated with using infectious viruses or isolating
membrane proteins, we will concurrently adapt existing cell-free synthesis (CFPS) techniques to
produce membrane proteins and efficiently insert them into our delivery vehicles of choice-
liposomes. The short-term goals of this project are to demonstrate 1) virus fusion-protein activity
and delivery, and 2) improved efficiency of virus membrane insertion into liposomes using the
adapted CFPS methodologies. The long-term goals include tuning the biodistribution capabilities,
afforded by the virus-derived proteins, to deliver cargo to discrete and specific locations within the
human body or other organism. This fellowship will provide the applicant with the financial support
needed to design and test the proteoliposome-based delivery system and develop ideas that will
aid the applicant's independent research program in the field of virus-inspired biomaterials.
Terms: <14-Hydroxydaunomycin><2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><Address><Adriamycine><Agriculture><Binding><Biocompatible Materials><Biodistribution><Biological><Biological Mimetics><Biomaterials><Biomimetics><Body Tissues><COVID-19 S protein><COVID-19 spike><COVID-19 spike glycoprotein><COVID-19 spike protein><Cell Body><Cell Communication><Cell Interaction><Cell Membrane Lipids><Cell Membrane Proteins><Cell membrane><Cell-to-Cell Interaction><Cells><Chimera Protein><Chimeric Proteins><Circulation><Communities><Cytoplasmic Membrane><Cytosol><Data><Doxorubicin><Doxorubicina><Drug Delivery><Drug Delivery Systems><Drug Targeting><Drugs><Elements><Encapsulated><Environment><Event><Fellowship><Financial Support><Fusion Protein><Future><Gene Delivery><Genes><Genetic><Glycoproteins><Goals><Health><Hemagglutinin><Human><Human Figure><Human body><Hydroxyl Daunorubicin><Hydroxyldaunorubicin><In Vitro><Influenza HA><Influenza Hemagglutinin><Integral Membrane Protein><Intrinsic Membrane Protein><Knowledge><Ligands><Lipid Bilayers><Lipids><Liposomal><Liposomes><Location><Mammalian Cell><Measurable><Medication><Medicine><Membrane><Membrane Lipids><Membrane Protein Gene><Membrane Proteins><Membrane-Associated Proteins><Methodology><Methods><Modeling><Modern Man><Molecular><Molecular Interaction><Nipah Virus><Nipah henipavirus><Organism><Outcome><Pathway interactions><Pharmaceutical Agent><Pharmaceutical Preparations><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Plasma Membrane><Production><Protein Biosynthesis><Proteins><Publishing><Reaction><Receptor Cell><Receptor Protein><Recurrence><Recurrent><Research><Ribosomal Peptide Biosynthesis><Ribosomal Protein Biosynthesis><Ribosomal Protein Synthesis><SARS-CoV-2 S><SARS-CoV-2 S protein><SARS-CoV-2 spike><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SRP><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Signal Recognition Particle><Specificity><Structure><Surface><Surface Proteins><System><Techniques><Technology><Temperature><Testing><Therapeutic><Tissues><Transmembrane Protein><Transmembrane Protein Gene><Vesicle><Viral><Viral Fusion Proteins><Viral Gene Products><Viral Gene Proteins><Viral Genome><Viral M Proteins><Viral Matrix Proteins><Viral Membrane Proteins><Viral Proteins><Virion><Virus><Virus Particle><Work><Zoonoses><Zoonotic><Zoonotic Infection><biologic><biological material><coronavirus disease 2019 S protein><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><delivery vector><delivery vehicle><design><designing><drug candidate><drug/agent><extracellular><financial assistance><flu HA><flu hemagglutinin><glycoprotein G><improved><influenza viral HA><influenza viral hemagglutinin><influenza virus HA><influenza virus hemagglutinin><lipid bilayer membrane><living system><membrane structure><nano particle><nano-sized particle><nanoparticle><nanosized particle><particle><pathogenic virus><pathway><pharmaceutical><plasmalemma><programs><protein synthesis><proteoliposomes><receptor><response><spike proteins on SARS-CoV-2><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><tool><uptake><viral genomics><viral pathogen><virus genome><virus genomics><virus pathogen><virus protein>