Nucleic acid-small diameter and liquid core nanoparticle complexed compositions
Inventors
Khandhar, Amit • Reed, Steven • DUTHIE, Malcolm • Erasmus, Jesse • Carter, Darrick • BERUBE, Bryan J.
Assignees
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Publication Number
US-11752218-B2
Publication Date
2023-09-12
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) nanoemulsion particles for nucleic acid delivery and imaging. The particles include a hydrophobic core comprising liquid oil in liquid phase at 25 degrees Celsius, where lipids in the hydrophobic core are present in liquid phase, and the core can include inorganic reporter nanoparticles for imaging.
In the disclosed composition, the LIONs comprise a surface comprising cationic lipids and a hydrophobic core that comprises liquid oil mixed with inorganic reporter nanoparticles. The nucleic acids are complexed to the cationic lipids to form nucleic acid–lipid nanoparticle complexes, including nucleic acids encoding an antibody to an antigen, and nucleic acids such as replicon/self-replicating RNA.
The inorganic components provide imaging capability via MRI contrast from the inorganic cores (T1/T2 contrast), while the lipid/inorganic nanoparticle structure supports nucleic acid protection and delivery. The disclosure reports enhanced delivery relative to nanostructured lipid carriers (NLC), along with RNase protection and sustained intracellular expression outcomes.
Claims Coverage
The independent claim coverage includes three inventive features: a nucleic-acid/antibody-encoding composition in lipid nanoparticles, a defined z-average diameter, and a liquid-oil hydrophobic core with nucleic acids complexed to cationic lipids.
Antibody-encoding nucleic acids complexed to cationic lipid nanoparticles
The composition includes nucleic acids comprising a sequence encoding for an antibody to an antigen, and nucleic acids are complexed to the cationic lipids to form nucleic acid–lipid nanoparticle complexes.
Defined z-average size lipid nanoparticles
The lipid nanoparticles have 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 of liquid oil
The lipid nanoparticles comprise a hydrophobic core, wherein the hydrophobic core comprises liquid oil, and lipids present in the hydrophobic core are in liquid phase at 25 degrees Celsius.
Across the independent claim coverage, the inventive concept is a composition of antibody-encoding nucleic acids complexed to cationic lipids within lipid nanoparticles having a defined 20–60 nm z-average size and a liquid-phase liquid-oil hydrophobic core.
Stated Advantages
Enhanced delivery compared to nanostructured lipid carriers (NLC).
Ability to track delivery via MRI using T1/T2 contrast from inorganic cores.
Protection of nucleic acids from RNases.
Sustained intracellular protein expression (reported via SEAP/antigen expression).
Documented Applications
Delivery of nucleic acids for antibody generation to antigens, including reported antibody generation against SARS-CoV-2, Zika virus, and RSV.
MRI imaging/tracking of delivery using inorganic nanoparticle cores providing T1/T2 contrast.
Use of replicon/self-replicating RNA as part of the nucleic acid cargo for delivery and expression.
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