# US 12,109,310 B2 · Exosome extracellular vesicles and methods of use > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,109,310 B2 - Document ID: US12109310B2 - Status: Granted - Kind: B2 - Application number: 16/972,190 - Filed: 2019-06-27 - Published: 2021-10-14 - Granted: 2024-10-08 - Earliest claimed: 2018-06-28 - Assignees: Hadi Valadi; Astraeneca AB - Applicants: AstraZeneca AB; Hadi Valadi - Inventors: Hadi Valadi; Lennart Lindfors - Web page: https://patentgrep.com/patent/US12109310B2 ## CPC - A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant - A61K 9/1272: comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543}) - A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911}) - A61K 31/7115: Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine - A61K 39/0005: {Vertebrate antigens (from snakes A61K39/38)} - A61K 2039/53: {DNA (RNA) vaccination} - A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract Exosomes comprising a modified RNA are disclosed. Aspects of the disclosure further relate to methods and compositions for using exosomes comprising a modified RNA. In certain aspects, the exosomes disclosed herein may be useful in delivering a modified RNA to a cell. In certain aspects, the exosomes disclosed herein may be useful in treating or preventing a disorder in a subject. Methods and compositions for producing the disclosed exosomes are also provided. ## Claims ### Claim 1 An isolated exosome comprising a modified ribonucleic acid (RNA) prepared by a process comprising: (a) providing one or more lipid nanoparticles (LNP) comprising the modified RNA; (b) contacting one or more cells with the LNP under conditions that allow LNP uptake by the one or more cells; and (c) isolating exosomes produced by the one or more cells, wherein at least one isolated exosome comprises the modified RNA; wherein the exosome comprises an ionizable lipid:modified RNA nucleotides molar ratio of about 1:1 to about 3:1, or less than about 1:1. ### Claim 2 (depends on 1) The isolated exosome of claim 1, wherein the LNP comprises at least one ionizable lipid, phospholipid, structural lipid, and/or PEG lipid, wherein the PEG lipid comprises a lipid portion and a polyethylene glycol portion. ### Claim 3 (depends on 1) The isolated exosome of claim 1, wherein the LNP comprises an ionizable lipid that is dilinoleylmethyl-4-dimethylaminobutyrate (DLin-MC3-DMA) or 1,2-dilinoleyloxy-3-dimethylaminopropane (DLin-DMA), a phospholipid that is 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), a structural lipid that is cholesterol, and/or a PEG lipid that is PEG-DMPE or PEG2000-DMPE. ### Claim 4 (depends on 1) The isolated exosome of claim 1, wherein the LNP comprises an ionizable lipid:modified RNA nucleotides molar ratio of about 2:1 to about 4:1. ### Claim 5 (depends on 1) The isolated exosome of claim 1, wherein the exosome comprises at least one ionizable lipid, phospholipid, structural lipid, and/or PEG lipid. ### Claim 6 (depends on 1) The isolated exosome of claim 1, wherein the exosome comprises an ionizable lipid:modified RNA nucleotides molar ratio of about 3:1, about 2:1, about 1:1, or less than about 1:1. ### Claim 7 (depends on 1) The isolated exosome of claim 1, wherein the exosome comprises an ionizable lipid:modified RNA nucleotides molar ratio of about 1:1 or less than about 1:1. ### Claim 8 (depends on 1) The isolated exosome of claim 1, wherein the exosome comprises an ionizable lipid:modified RNA nucleotides molar ratio that is less than the ionizable lipid:modified RNA nucleotides molar ratio comprised by the LNP. ### Claim 9 (depends on 1) The isolated exosome of claim 1, wherein the one or more cells are is obtained from a subject. ### Claim 10 (depends on 1) The isolated exosome of claim 1, wherein the one or more cells are is an epithelial cells, immune cells, progenitor cells, or stem cells. ### Claim 11 (depends on 1) The isolated exosome of claim 1, wherein the process is performed in vitro. ### Claim 12 (depends on 1) The isolated exosome of claim 1, wherein isolating exosomes comprises isolating exosomes from a sample of in vitro cell culture medium. ### Claim 13 (depends on 1) A pharmaceutical composition comprising at least one isolated exosome of claim 1, and a pharmaceutically acceptable carrier. ### Claim 14 (depends on 1) A method of treating or preventing a disorder in a subject, comprising administering to the subject an effective amount of the isolated exosomes of claim 1, wherein the isolated exosomes comprise a modified RNA effective to treat the disorder. ### Claim 15 (depends on 14) The method of claim 14, wherein the subject has a reduced immune and/or inflammatory response to treatment in the presence of an isolated exosome as compared to treatment in the absence of an isolated exosome. ### Claim 16 (depends on 14) The method of claim 14, wherein the isolated exosomes are isolated from a cell obtained from the subject.