Compositions and methods for delivery of nucleic acid-lipid nanoparticle complexes encoding for viral RNA polymerase region and protein antigen
Inventors
Khandhar, Amit • Reed, Steven • DUTHIE, Malcolm • Erasmus, Jesse • Carter, Darrick • BERUBE, Bryan J.
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Assignees
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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-11458209-B2
Publication Date
2022-10-04
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. Compositions of the disclosure include nucleic-acid lipid nanoparticle complexes encoding for viral RNA polymerase region and protein antigen. The nanoemulsion compositions of the disclosure comprises a hydrophobic core, optionally including 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, including methods for administering to a subject a composition of the disclosure in an amount sufficient to generate an immune response.
Core Innovation
The invention discloses lipid InOrganic Nanoparticles (LIONs) formulated in nanoemulsion form for delivering nucleic acids to generate an immune response. The nucleic-acid payload includes nucleic acids encoding protein antigens, including viral antigens, and replicon RNAs, and the nucleic acids are complexed with nanoparticles to form nucleic acid-nanoparticle complexes for delivery to a subject.
The nanoparticles include a hydrophobic core comprising a mixture of liquid oil and a solid inorganic nanoparticle, combined with a cationic lipid. The formulation further includes a hydrophilic surfactant and a hydrophobic surfactant. The inorganic component comprises inorganic reporter nanoparticles that enable imaging and tracking, including magnetic resonance imaging using magnetic iron oxides.
The disclosed LION-based compositions protect RNA from RNase degradation and improve cytoplasmic expression of delivered replicon mRNA. In vivo, the compositions enhance antigen-specific antibody responses and can induce Th1-biased and neutralizing responses in animal models. The document also reports MRI contrast enhancement and innate immune activation using RNA PAMPs delivered via LIONs.
Claims Coverage
The provided claim material identifies one independent claim. It covers administering a composition sufficient to generate an immune response, where nucleic acids encoding a protein antigen are complexed with nanoparticles having a specific nanoparticle architecture and surfactant/lipid components.
Immune-response administration of nucleic acid encoding a protein antigen complexed with LION nanoparticles
Administering to a subject a composition sufficient to generate an immune response, wherein the composition comprises nanoparticles with a hydrophobic core comprising a mixture of liquid oil and a solid inorganic nanoparticle, a cationic lipid, a hydrophilic surfactant, and a hydrophobic surfactant, and wherein nucleic acids encoding for a protein antigen are complexed with the nanoparticles to form nucleic acid-nanoparticle complexes.
Nanoparticles with liquid oil plus solid inorganic nanoparticle hydrophobic core
The nanoparticles comprise a hydrophobic core comprising a mixture of liquid oil and a solid inorganic nanoparticle.
Cationic lipid and surfactants included in nanoparticle composition
The nanoparticles include a cationic lipid, a hydrophilic surfactant, and a hydrophobic surfactant.
Across the provided claim material, the core coverage is an immune-response method using nucleic acid-nanoparticle complexes formed with nanoparticles that combine a liquid-oil/solid-inorganic hydrophobic core with a cationic lipid and both hydrophilic and hydrophobic surfactants.
Stated Advantages
Protects RNA from RNase degradation.
Improves cytoplasmic expression of delivered replicon mRNA.
Enhances antigen-specific antibody responses.
Induces Th1-biased and neutralizing responses in animal models.
Provides imaging/tracking, including MRI contrast enhancement.
Activates innate immune responses using RNA PAMPs delivered via LIONs.
Documented Applications
Delivery of nucleic acids encoding viral antigens, including SARS-CoV-2 spike/RBD, Zika candidates, and RSV F and G (A2) candidates, using LION nanoparticles to generate immune responses.
Delivery of replicon RNAs, including replicon mRNA, to enhance expression and immune responses.
MRI contrast enhancement and imaging/tracking based on the inorganic reporter component, including magnetic iron oxides.
Innate immune activation using RNA PAMPs delivered via LIONs, including a RIG-I agonist PAMP and a TLR3 agonist.
In vitro delivery for replicon RNA, including nLuc, using LION nanoparticles and reporting IFN-β promoter activation and IFIT2.
Animal model studies in mice, rabbits, and nonhuman primates for immune response generation and associated readouts.
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