RNA-lipid nanoparticle complexes of viral RNA polymerase region and SARS-CoV-2 spike protein region
Inventors
Khandhar, Amit • Reed, Steven • DUTHIE, Malcolm • Erasmus, Jesse • Carter, Darrick • BERUBE, Bryan J.
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Assignees
Member
HDT BioHDT Bio is a clinical-stage biopharmaceutical company based in Seattle, developing novel technologies and products designed to harness and enhance the immune system for the treatment and prevention of cancer and infectious diseases. HDT Bio utilizes advanced immunotherapeutic platforms, including a proprietary nanoparticle delivery system, to provide safe, potent, and durable solutions that enable rapid clinical translation and personalized cancer therapies. The company's multidisciplinary team and international partnerships facilitate robust clinical development, innovative product design, and global distribution with the goal of improving patient outcomes worldwide.
HDT Bio is a clinical-stage biopharmaceutical company based in Seattle, developing novel technologies and products designed to harness and enhance the immune system for the treatment and prevention of cancer and infectious diseases. HDT Bio utilizes advanced immunotherapeutic platforms, including a proprietary nanoparticle delivery system, to provide safe, potent, and durable solutions that enable rapid clinical translation and personalized cancer therapies. The company's multidisciplinary team and international partnerships facilitate robust clinical development, innovative product design, and global distribution with the goal of improving patient outcomes worldwide.
Publication Number
US-11376335-B2
Publication Date
2022-07-05
Expiration Date
Abstract
The disclosure provides nanoemulsion compositions and methods of making and using thereof to deliver a bioactive agent such as a nucleic acid to a subject. The nanoemulsion composition comprises a hydrophobic core based on inorganic nanoparticles in a lipid nanoparticle that allows imaging as well as delivering nucleic acids. Methods of using these particles for treatment and vaccination are also provided.
Core Innovation
The invention provides a composition that comprises RNA molecules and lipid nanoparticles, where the RNA molecules comprise sequence encoding for an RNA polymerase complex region from an RNA virus and a SARS-CoV-2 spike protein region. The lipid nanoparticles comprise a surface comprising cationic lipids and a hydrophobic core, and the RNA molecules are complexed to the cationic lipids to form RNA molecule-lipid nanoparticle complexes.
The described lipid inorganic nanoparticle (LION) nanoemulsion composition combines an inorganic nanoparticle hydrophobic core with lipid and surfactant components. The inorganic core includes reporter-containing materials such as iron oxide SPIO for MRI, and the lipid/surfactant matrix includes cationic lipids for complexation of RNA molecules, providing intracellular translation/antigen expression as described in the document.
The invention further relates to the use of the RNA-lipid nanoparticle composition for delivering self-replicating repRNA encoding antigens and for enabling imaging and tracking by MRI based on the inorganic core. The document also describes compositions and examples in which the RNA includes a SARS-CoV-2 spike region and an RNA virus RNA polymerase complex region, and the lipid nanoparticle includes defined cationic lipids and surfactant systems, including combinations such as DOTAP with specific oils and surfactants.
Claims Coverage
The independent claim covers an RNA molecule–lipid nanoparticle composition with two encoded regions (an RNA virus RNA polymerase complex region and a SARS-CoV-2 spike protein region) and a lipid nanoparticle having a cationic-lipid surface and a hydrophobic core, with the RNA complexed to the cationic lipids. Across the dependent claims, the number of inventive features includes defining the hydrophobic core material class, narrowing the encoded sequence details, and specifying cationic lipid and surfactant component selections.
RNA molecules encoding an RNA polymerase complex region and a SARS-CoV-2 spike protein region
The composition includes RNA molecules with sequence encoding for an RNA polymerase complex region from an RNA virus and a SARS-CoV-2 spike protein region.
Cationic lipid surface complexing RNA
The lipid nanoparticles include a surface comprising cationic lipids, and the RNA molecules are complexed to the cationic lipids to form RNA molecule-lipid nanoparticle complexes.
Hydrophobic core in lipid nanoparticles
The lipid nanoparticles comprise a hydrophobic core in addition to the cationic lipid surface.
Solid inorganic nanoparticle hydrophobic core
The lipid nanoparticles include a hydrophobic core made of a solid inorganic nanoparticle.
Specific iron oxide polymorph options for the core
The hydrophobic core includes an iron oxide component selected from magnetite (Fe3O4), maghemite (γ-Fe2O3), wustite (FeO), hematite (α-Fe2O3), or any combination of these.
Liquid oil or solid lipid hydrophobic core selection
The hydrophobic core includes a liquid oil component selected from a vegetable oil, an animal oil, or a synthetically prepared oil.
SARS-CoV-2 spike region derived from a specific isolate
The sequence encoding for the SARS-CoV-2 spike protein region is derived from the SARS-CoV-2 isolate Wuhan-Hu-1.
DOTAP with defined additional components
The cationic lipids are DOTAP, and the lipid nanoparticles also include squalene, sorbitan monostearate, and polysorbate 80.
Overall, the claim set focuses on RNA molecules that encode an RNA polymerase complex region and a SARS-CoV-2 spike protein region, delivered as RNA molecule-lipid nanoparticle complexes using lipid nanoparticles with a cationic-lipid surface and a hydrophobic core. Dependent limitations further specify hydrophobic core material selections (solid inorganic nanoparticle classes including iron oxide polymorph options, or liquid oil choices), narrow the spike-region isolate source, and specify defined cationic lipid and formulation component selections such as DOTAP with squalene and particular surfactants.
Stated Advantages
MRI imaging/tracking enabled by the inorganic reporter-containing hydrophobic core.
Improved RNA delivery and stability compared with naked RNA.
Intracellular translation/antigen expression based on the RNA molecule-lipid nanoparticle complexes.
Protection of RNA from RNase degradation as described in the document.
In vivo expression of SEAP and/or antigen as described in examples.
Documented Applications
Delivery of self-replicating repRNA encoding antigens, including SARS-CoV-2 spike, with intracellular expression as described.
Use of the compositions for MRI imaging/tracking based on an inorganic reporter-containing core.
In vivo and preclinical evaluations including mice, aged models, and nonhuman primates as described in the document examples.
Immune activation described in relation to delivery of a RIG-I agonist (PAMP) and a TLR3 agonist (Riboxxim) using the lipid nanoparticle compositions.
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