Hybridosomes, compositions comprising the same, processes for their production and uses thereof

1. A hybridosome comprising a therapeutic agent encapsulated by a membrane of the hybridosome; wherein the membrane of the hybridosome comprises:

a. elements of a membrane of a first vesicle, wherein the elements of a membrane of the first vesicle comprise a fusogenic, ionizable cationic lipid, wherein said fusogenic, ionizable cationic lipid has at least one protonatable or deprotonatable group, such that the lipid is positively charged at a pH and neutral above the pH, and wherein said first vesicle has been produced in vitro such that the fusogenic, ionizable cationic lipid is present at a molar concentration of at least 30% of total lipid of the first vesicle; and

b. elements of a lipid bilayer of a second vesicle, wherein said second vesicle has been produced in vivo and is released into the extracellular environment.

2. The hybridosome of claim 1 , wherein

a. the first vesicle is selected from the group consisting of lipid-based nanoparticles (LNPs), liposomes, polymer-stabilized LNPs, cerasomes, sphingosomes, polymersomes, synthetic-nanoparticle stabilized LNPs, natural membrane-derived LNPs, and natural membrane-coated LNPs; and

b. the second vesicle is selected from the group consisting of an exosome, ectosome, microvesicle, or apoptotic body.

3. The hybridosome of claim 1 , wherein

a. the first vesicle is an LNP; or

b. the second vesicle is an exosome.

4. The hybridosome of claim 1 , wherein

a. the first vesicle is an LNP; and

b. the second vesicle is an exosome.

5. The hybridosome of claim 1 wherein the hybridosome comprises a lipid of an exosome, ectosome, microvesicle, or apoptotic body.

6. The hybridosome of claim 5 , wherein the exosome, ectosome, microvesicle, or apoptotic body is a naturally secreted exosome, ectosome, microvesicle or apoptotic body.

7. The hybridosome of claim 1 , wherein the fusogenic, ionizable cationic lipid is selected from the group consisting of 1,2-Dilinoleyloxy-N,N-dimethylaminopropane (DLinDMA), 2,2-dilinoleyl-4-(2-dimethylaminoethyl)-[1,3]-dioxolane (DLin-KC2-DMA), heptatriaconta-6,9,28,31-tetraen-19-yl4-(dimethylamino)butanoate (DLin-MC3-DMA), 1,2-dioleoyl-3-dimethylammonium-propane (DODAP), N-(4-carboxybenzyl)-N,N-dimethyl-2,3-bis(oleoyloxy)propan-1-aminium (DOBAQ), YSKO5, 4-(((2,3-bis(oleoyloxy)propyl)-(methyl)amino)methyl)benzoic acid (DOBAT), N-(4-carboxybenzyl)-N,N-dimethyl-2,3-bis(oleoyloxy)propan-1-aminium (DOBAQ), 3-((2,3-bis(oleoyloxy)propyl)(methyl)amino)propanoic acid (DOPAT), N-(2-carboxypropyl)-N,N-dimethyl-2,3-bis-(oleoyloxy)-propan-1-aminium (DOMPAQ), N-(carboxymethyl)-N,N-dimethyl-2,3-bis(oleoyloxy)propan-1-aminium (DOAAQ), Alny-100, 3-(dimethylamino)-propyl(12Z,15Z)-3-[(9Z,12Z)-octadeca-9,12-dien-1-yl]-henicosa-12,15-dienoate (DMAP-BLP), and derivatives of ionizable amino-lipids.

8. The hybridosome of claim 1 wherein the hybridosome further comprises a targeting moiety selected from the group consisting of antibodies or fragments thereof, antibody-like molecules, peptides, proteins, aptamers, oligonucleotides, sugars, polysaccharides and vitamins.

9. The hybridosome of claim 8 , wherein said targeting moiety binds to a moiety on the cell surface of a target cell.

10. The hybridosome of claim 1 wherein the hybridosome further comprises a fusion peptide anchored to its surface, wherein said fusion peptide is selected from soluble N-ethyl maleimide sensitive factor attachment protein receptors (SNARE proteins) and synthetics mimics thereof.

11. The hybridosome of claim 1 wherein the hybridosome further comprises a PEG-modified lipid.

12. The hybridosome of claim 1 , wherein the therapeutic agent is:

a. a drug or a pharmaceutically acceptable salt or derivative thereof;

b. an antibody-based therapeutic agent; or

c. a peptide, a protein, or a nucleic acid.