Compositions and methods for delivery of RNA-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.

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 RNA-lipid nanoparticle complexes encoding for viral RNA polymerase region and protein antigen. Compositions are further described where the lipid nanoparticles are characterized as having a z-average diameter particle size measurement of 20 nm to 80 nm when measured using dynamic light scattering. 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.

Core Innovation

The invention provides a composition comprising RNA molecules and lipid nanoparticles, where the RNA molecules comprise a sequence encoding an RNA polymerase complex region from an RNA virus and a protein antigen. The RNA molecules are complexed to cationic lipids to form RNA-lipid nanoparticle complexes. The lipid nanoparticles are characterized by a z-average diameter particle size measurement of 20 nm to 80 nm when measured using dynamic light scattering.

The lipid nanoparticles comprise a surface comprising cationic lipids and a hydrophobic core. The hydrophobic core comprises liquid oil, and the lipids present in the hydrophobic core are in liquid phase at 25 degrees Celsius. In the described system context, the lipid inorganic nanoparticle approach is used to deliver RNA encoding viral RNA polymerase regions and protein antigens, including replicon RNA.

Inorganic MRI/imaging-detectable nanoparticles can be included within the hydrophobic core alongside the liquid oil, and the resulting compositions are associated with RNase protection, in vivo protein expression from the RNA, and MRI contrast enhancement through T1/T2 relaxivity measures. The described embodiments further include RNA formats that can stimulate innate immune responses, including immunomodulating RNAs such as RIG-I agonist PAMP and a TLR3 agonist.

Claims Coverage

The partial claims provided include one independent claim. The inventive features include defining the RNA target and protein antigen together with lipid nanoparticle physical and chemical characteristics.

Across the provided independent claim, the coverage centers on RNA-lipid nanoparticle complexes that co-present an RNA virus polymerase complex region and a protein antigen, using lipid nanoparticles with a DLS-measured z-average size between 20 nm and 80 nm, a cationic lipid surface, and a hydrophobic oil core with lipids in liquid phase at 25 degrees Celsius.

Stated Advantages

Documented Applications