RNA-lipid nanoparticle complexes of viral RNA polymerase region and SARS-CoV-2 spike protein region
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.
1. A composition, wherein the composition comprises:
RNA molecules, wherein the RNA molecules comprise sequence encoding for:
an RNA polymerase complex region from an RNA virus; and
a SARS-CoV-2 spike protein region; and
lipid nanoparticles, wherein the lipid nanoparticles comprise:
a surface comprising cationic lipids; and
a hydrophobic core, and
wherein the RNA molecules are complexed to the cationic lipids to form RNA molecule-lipid nanoparticle complexes.
2. The composition of claim 1 , wherein the RNA virus is a Venezuelan equine encephalitis virus.
3. The composition of claim 2 , wherein the Venezuelan equine encephalitis virus is strain TC-83.
4. The composition of claim 2 , wherein the sequence encoding for the RNA polymerase comprises sequence encoding for nsP1-4.
5. The composition of claim 1 , wherein the sequence encoding for the SARS-CoV-2 spike protein region comprises S1, S2, transmembrane, and cytoplasmic domain sequence.
6. The composition of claim 1 , wherein the sequence encoding for the SARS-CoV-2 spike protein region comprises sequence from SARS-CoV-2 isolate Wuhan-Hu-1.
7. The composition of claim 1 , wherein the hydrophobic core comprises a lipid.
8. The composition of claim 1 , wherein the cationic lipids are selected from the group consisting of 1,2-dioleoyloxy-3-(trimethylammonium)propane (DOTAP); 3b-[N—(N′,N′-dimethylaminoethane)-carbamoyl]cholesterol (DC Cholesterol); dimethyldioctadecylammonium (DDA); 1,2-dimyristoyl-3-trimethylammoniumpropane (DMTAP), dipalmitoyl(C16:0)trimethyl ammonium propane (DPTAP); distearoyltrimethylammonium propane (DSTAP); N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA); N,N-dioleoyl-N,N-dimethylammonium chloride (DODAC); 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC); 1,2-dioleoyl-3-dimethylammonium-propane (DODAP); and 1,2-dilinoleyloxy-3-dimethylaminopropane (DLinDMA); and 1, r-((2-(4-(2-((2-(bis(2-hydroxydodecyl)amino)ethyl) (2-hydroxydodecyl)amino)ethyl)piperazin-1-ypethyl)azanediyl)bis(dodecan-2-ol) (C 12-200).
9. The composition of claim 1 , wherein the cationic lipids are DOTAP.
10. The composition of claim 1 , wherein the hydrophobic core comprises a solid inorganic nanoparticle.
11. The composition of claim 10 , wherein the solid inorganic nanoparticle is selected from the group consisting of metal salts, metal oxides, metal hydroxides, and metal phosphates.
12. The composition of claim 10 , wherein the solid inorganic nanoparticle comprises iron oxide.
13. The composition of claim 12 , wherein the iron oxide is magnetite (Fe 3 O 4 ), maghemite (y-Fe 2 O 3 ), wustite (FeO), hematite (a-Fe 2 O 3 ), or any combination thereof.
14. The composition of claim 1 , wherein the hydrophobic core comprises liquid oil.
15. The composition of claim 14 , wherein the hydrophobic core further comprises a solid lipid.
16. The composition of claim 15 , wherein the solid lipid comprises glyceryl trimyristate.
17. The composition of claim 14 , wherein the liquid oil is a vegetable oil, an animal oil, or a synthetically prepared oil.
18. The composition of claim 14 , wherein the liquid oil is capric/caprylic triglyceride, vitamin E, lauroyl polyoxylglyceride, monoacylglycerol, sunflower oil, soybean oil, olive oil, grapeseed oil, or any combination thereof.
19. The composition of claim 14 , wherein the liquid oil is squalene.
20. The composition of claim 1 , wherein the lipid nanoparticles further comprise a hydrophobic surfactant and a hydrophilic surfactant.
21. The composition of claim 20 , wherein the hydrophobic surfactant is selected from the group consisting of sorbitan monostearate, sorbitan monooleate, and sorbitan trioleate.
22. The composition of claim 20 , wherein the hydrophilic surfactant comprises polyethylene oxide.
23. The composition of claim 22 , wherein the polyethylene oxide comprises polyoxyethylene sorbitan ester.
24. The composition of claim 20 , wherein the hydrophilic surfactant comprises polysorbate.
25. The composition of claim 24 , wherein the polysorbate comprises polysorbate 80.
26. The composition of claim 1 , wherein the cationic lipids comprise DOTAP, and wherein the lipid nanoparticles further comprise: squalene, sorbitan monostearate, and polysorbate 80.
27. The composition of claim 26 , wherein the composition further comprises sodium citrate.
28. The composition of claim 26 , wherein the hydrophobic core further comprises solid iron oxide.
29. The composition of claim 28 , wherein the composition further comprises sodium citrate.