Compositions and methods for delivery of RNA
Inventors
Khandhar, Amit • Reed, Steven • DUTHIE, Malcolm • Erasmus, Jesse • Carter, Darrick • BERUBE, Bryan J.
Assignees
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Publication Number
US-11654200-B2
Publication Date
2023-05-23
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 administering a composition for delivering nucleic acids to a subject for generating an immune response with enhanced safety. The composition comprises lipid nanoparticles characterized by a z-average diameter particle size measurement of about 20 nm to about 60 nm when measured using dynamic light scattering, and the lipid nanoparticles comprise a hydrophobic core comprising lipids present in liquid phase at 25 degrees Celsius. The nucleic acids are complexed to the lipid nanoparticles to form nucleic acid-lipid nanoparticle complexes.
The described system is contrasted against a composition in which the nucleic acids are encapsulated in the lipid nanoparticles. Enhanced safety is characterized by a reduction in systemic adverse reactions compared to that encapsulated-nucleic-acid formulation. The description further indicates that nucleic acids are protected from RNases and are delivered to support protein expression and immune activation.
The described lipid nanoparticle platform is further characterized as including inorganic nanoparticle hydrophobic cores embedded in a lipid matrix, forming lipid inOrganic nanoparticles (LIONs). Inorganic cores may include iron oxide for MRI contrast or aluminum hydroxide/oxyhydroxide cores, and the lipid matrix includes cationic lipid and optionally surfactants. The description also supports imaging and tracking using magnetic resonance imaging contrast based on the inorganic component, while the nucleic acid delivery is associated with innate immune activation and antigen-specific antibody responses.
Claims Coverage
The independent claim set centers on a nucleic-acid delivery method using lipid nanoparticles with defined particle-size characterization and a liquid-phase hydrophobic core, where nucleic acids are complexed to form nucleic acid-lipid nanoparticle complexes. In the provided claim content, four inventive features are expressly presented across the independent and dependent claim language.
Immune-response nucleic-acid delivery with enhanced safety via complexed nucleic acids
A method for delivering nucleic acids for generating an immune response with enhanced safety, comprising administering to a subject a composition where nucleic acids are complexed to lipid nanoparticles to form nucleic acid-lipid nanoparticle complexes, and the administering provides enhanced safety characterized by a reduction in systemic adverse reactions compared to administration of a composition wherein the nucleic acids are encapsulated in the lipid nanoparticles.
Lipid nanoparticles with z-average 20 nm to 60 nm by dynamic light scattering
A composition where the lipid nanoparticles are characterized as having a z-average diameter particle size measurement of about 20 nm to about 60 nm when measured using dynamic light scattering.
Liquid-phase hydrophobic core at 25 degrees Celsius
A composition where the lipid nanoparticles comprise a hydrophobic core comprising lipids present in liquid phase at 25 degrees Celsius.
Hydrophobic core including a solid inorganic nanoparticle
A method where the hydrophobic core contains a solid inorganic nanoparticle, with the surface optionally comprising both a hydrophobic surfactant and a hydrophilic surfactant.
The core inventive coverage centers on administering lipid nanoparticles that meet defined physical characterization, with nucleic acids complexed to the nanoparticles, to generate an immune response with enhanced safety. The additional claim language further defines particle-size, liquid-phase core, and inorganic-core or surfactant features.
Stated Advantages
Enhanced safety characterized by a reduction in systemic adverse reactions compared to administration of a composition wherein the nucleic acids are encapsulated in the lipid nanoparticles.
Induces a greater Th1-biased than a Th2-biased immune response.
Documented Applications
Generating an immune response in a subject using nucleic acids delivered by lipid nanoparticles.
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