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-11318213-B2
Publication Date
2022-05-03
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
A nanoemulsion composition is disclosed in which nanoemulsion particles include a hydrophobic core comprising a mixture of a liquid oil and a solid inorganic nanoparticle, together with a cationic lipid, a hydrophilic surfactant, and a hydrophobic surfactant. The composition further includes a nucleic acid that is complexed with the nanoemulsion particles and modulates innate immune response.
The nucleic acid in the nanoemulsion particles includes RNA, repRNA, and other RNAs, and is associated with innate immune activation, including PAMP-mediated signaling, RIG-I agonist activity, and TLR agonist activity. The complexed nucleic acid is used to elicit protein expression and immune responses as described in the disclosed experimental support.
The nanoemulsion particles are further characterized by a mixture of inorganic reporter nanoparticles within the hydrophobic core, including MRI-detectable iron oxides and TOPO-coated Al oxyhydroxide. The described formulations are associated with improved RNA protection from RNases, enhanced protein expression, magnetic resonance contrast enhancement, and innate immune activation with subsequent antibody responses, including Th1-biased immune responses as reported.
Claims Coverage
The partial content identifies one independent claim. The claim covers a nanoemulsion composition defined by a hydrophobic core of liquid oil and solid inorganic nanoparticle, a cationic lipid, a hydrophilic surfactant, a hydrophobic surfactant, and a nucleic acid complexed with the nanoemulsion particles to modulate innate immune response.
Hydrophobic core with liquid oil and solid inorganic nanoparticle
The nanoemulsion particles include a hydrophobic core comprising a mixture of a liquid oil and a solid inorganic nanoparticle.
Cationic lipid in nanoemulsion particles
The nanoemulsion particles include a cationic lipid.
Hydrophilic and hydrophobic surfactants in nanoemulsion particles
The nanoemulsion particles include a hydrophilic surfactant and a hydrophobic surfactant.
Nucleic acid complexed to modulate innate immune response
The nanoemulsion composition includes a nucleic acid complexed with the nanoemulsion particles, wherein the nucleic acid modulates innate immune response.
Overall, the claim coverage centers on a nanoemulsion particle architecture that combines a liquid-oil/solid-inorganic hydrophobic core with cationic lipid plus both surfactant types, and that presents a nucleic acid complexed to the particles to modulate innate immune response. Dependent claim refinements further narrow inorganic nanoparticle chemistry options, particle size, receptor-targeting of innate immune modulation, and optional formulation components such as sodium citrate.
Stated Advantages
Improved RNA protection from RNases.
Enhanced SEAP and antigen/protein expression in vivo.
Maintained antigen bioactivity across inorganic core sizes.
Superior delivery compared to nanostructured lipid carrier (NLC) control.
MRI contrast enhancement via T1/T2 relaxivity.
Induced antibody and Th1-biased immune responses, including neutralization.
Innate immune activation by PAMP signaling, including RIG-I agonist and TLR3 agonist activity when delivered by LION.
Documented Applications
Delivering nucleic acids (RNA/repRNA and other RNAs) to elicit protein expression and immune responses.
Magnetic resonance imaging (MRI) contrast enhancement associated with the nanoemulsion delivery system.
Inducing gene expression and innate immune activation following intranasal delivery as described in the experimental support.
Immunization/antigen delivery leading to antibody responses and Th1-biased immune responses as described in mice, rabbits, and nonhuman primates.
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