Compositions and methods for delivery of RNA
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-11559584-B2
Publication Date
2023-01-24
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 relates to lipid InOrganic Nanoparticles (LION) nanoemulsions for nucleic acid (RNA) delivery, including nucleic acid-lipid nanoparticle complexes in which nucleic acids complex to cationic lipids. The disclosed particles include a hydrophobic oil core containing inorganic reporter nanoparticles, such as iron oxide (SPIO) or inorganic materials like TOPO-coated aluminum hydroxide/oxyhydroxide, and this combination supports RNA delivery while providing imaging capability.
The disclosed nucleic acids include RNA that encodes an RNA polymerase complex region from an RNA virus and a SARS-CoV-2 spike protein region. The nucleic acids are complexed to a lipid nanoparticle surface comprising cationic lipids, forming nucleic acid-lipid nanoparticle complexes. The described system is intended to protect nucleic acids from RNases and promote enhanced expression of encoded proteins.
The described LION formulation is characterized by imaging contrast, including magnetic resonance imaging with T1/T2 contrast for tracking. In the documented experiments, the system is evaluated for protein expression and immune outcomes after delivery, including antibody generation and innate immune activation assays. The disclosed use includes applications consistent with vaccine and immunogenicity outcomes.
Claims Coverage
The partial independent claim clm-00001 covers one inventive feature: a manufacturing method that forms nucleic acid-lipid nanoparticle complexes by mixing nucleic acids encoding an RNA polymerase complex region from an RNA virus and a SARS-CoV-2 spike protein region with lipid nanoparticles having a cationic-lipid surface and a hydrophobic core, such that the nucleic acids complex to the cationic lipids. No other independent claim text is provided in the partial content received.
Manufacturing nucleic acid-lipid nanoparticle complexes by complexing to a cationic-lipid surface
Mixing nucleic acids that comprise sequence encoding an RNA polymerase complex region from an RNA virus and a SARS-CoV-2 spike protein region with lipid nanoparticles having a surface comprising cationic lipids and a hydrophobic core, wherein the nucleic acids complex to the cationic lipids to form nucleic acid-lipid nanoparticle complexes.
Based on the partial content, coverage centers on the manufacturing method where specific nucleic acid sequence regions are complexed to cationic lipids on lipid nanoparticles with a hydrophobic core.
Stated Advantages
Protects RNA from RNases.
Enhances expression of encoded proteins.
Provides imaging capability for tracking by MRI with T1/T2 contrast.
Supports vaccine and immunogenicity outcomes, including Th1-biased immune response and neutralizing antibodies.
Documented Applications
Vaccine/immunogenicity applications evaluated with RNA virus-related encoding, including SARS-CoV-2 spike repRNA, and reported neutralizing antibody and Th1-biased responses.
MRI-based tracking using T1/T2 contrast from the disclosed imaging-capable formulation.
In vitro delivery evaluation using reporter expression (nLuc) described in the partial content.
Innate immune activation evaluation using assays described in the partial content.
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