Compositions and methods for delivery of RNA

Inventors

Khandhar, Amit • Reed, Steven • DUTHIE, Malcolm • Erasmus, Jesse • Carter, Darrick • BERUBE, Bryan J.

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 disclosure describes lipid-based nanoparticle compositions for delivering nucleic acids, including RNA, to generate an immune response in a subject. The compositions include lipid nanoparticles with a hydrophobic core and a surface comprising cationic lipids, where the nucleic acids are complexed to the cationic lipids to form nucleic acid–lipid nanoparticle complexes.

The nucleic acids comprise sequence encoding for an RNA polymerase complex region from an RNA virus and for a SARS-CoV-2 spike protein region. The disclosure further provides that the RNA polymerase complex region and the SARS-CoV-2 spike protein region are delivered as part of nucleic acid payloads complexed to cationic lipids.

The lipid nanoparticle compositions are also described as including a hydrophobic oil core and an inorganic component contained within a lipid matrix, where the inorganic component is an MRI-detectable nanoparticle. The inorganic reporter enables imaging and tracking by magnetic resonance imaging, including T1/T2 contrast, and the resulting intracellular expression and immune activation include generation of adaptive immune responses and antigen-specific adaptive immune responses.

Claims Coverage

Independent inventive claim clm-00001 defines a method for generating an immune response by administering a nucleic acid–cationic lipid nanoparticle complex. The claim includes three principal inventive features: the nanoparticle structure, the nucleic acid payload, and the complexation of the nucleic acids to cationic lipids.

Across the independent claim, the core coverage is directed to administering nucleic acids encoding an RNA virus RNA polymerase complex region and a SARS-CoV-2 spike protein region in lipid nanoparticles that present cationic lipids on the surface and a hydrophobic core, with nucleic acid complexation to the cationic lipids to form nucleic acid–lipid nanoparticle complexes.

Stated Advantages

Documented Applications