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AssigneeChildren's Hospital Medical Center
InventorsDouglas MILLAY, Sajedah HINDI
Estimating the term…
Some embodiments of the invention include pseudotyped particles (e.g., pseudo typed exosomes, pseudotyped VSV, and pseudo typed lentiviruses) and modified cells. Other embodiments of the invention include compositions (e.g., pharmaceutical compositions) of pseudotyped particles (e.g., pseudotyped exosomes, pseudotyped VSV, and pseudotyped lentiviruses) and modified cells. Certain embodiments of the invention include methods of making pseudotyped particles (e.g., pseudotyped exosomes, pseudotyped VSV, and pseudotyped lentiviruses) and modified cells. Other embodiments of the invention include methods of administering pseudotyped particles (e.g., pseudotyped exosomes, pseudotyped VSV, and pseudotyped lentiviruses). Further embodiments of the invention include methods of administering pseudotyped particles (e.g., pseudotyped exosomes, pseudotyped VSV, and pseudotyped lentiviruses) to treat diseases (e.g., muscular dystrophy). Additional embodiments of the invention are also discussed herein.
A pseudotyped particle selected from the group consisting of pseudotyped exosomes and pseudotyped viruses, wherein the pseudotyped particle comprises one or more polypeptides and the one or more polypeptides comprises one or more myomaker polypeptides, one or more myomerger polypeptides, or a combination thereof.
The pseudotyped particle of any of the preceding claims, wherein one or more myomaker polypeptides, one or more myomerger polypeptides, or a combination thereof is present on the lipid envelope of the pseudotyped particle.
The lipid particle of any of the preceding claims, wherein the lipid particle has a size of 20-500 nm, optionally 30-150 nm or 80-120 nm.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle does not comprise any nucleic acid encoding a myomaker protein and/or a myomerger protein.
The pseudotyped particle of any of the preceding claims, wherein (a) the pseudotyped particle has one or more polypeptides on the pseudotyped particle's surface that are not found in the corresponding naturally occurring particle, (b) the pseudotyped particle has a larger amount of one or more polypeptides on the pseudotyped particle's surface than that found in the corresponding naturally occurring particle, (c) the pseudotyped particle has a larger amount of one or more polypeptides in the pseudotyped particle, by measuring the total amount of polypeptide in the pseudotyped particle, than that found in the corresponding naturally occurring particle, or (d) a combination of (a), (b), or (c).
The pseudotyped particle of any of the preceding claims, wherein (a) the pseudotyped particle has one or more polypeptides on the pseudotyped particle's surface that are not found in the corresponding non-pseudotyped particle, (b) the pseudotyped particle has a larger amount of one or more polypeptides on the pseudotyped particle's surface than that found in the corresponding non-pseudotyped particle, (c) the pseudotyped particle has a larger amount of one or more polypeptides in the pseudotyped particle, by measuring the total amount of polypeptide in the pseudotyped particle, than that found in the corresponding non-pseudotyped particle, or (d) a combination of (a), (b), or (c).
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle is selected from a pseudotyped exosome, a pseudotyped VSV, and a pseudotyped lentivirus.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle is a pseudotyped exosome.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle is a pseudotyped exosome and the exosome is produced from an exosome producing cell that expresses or overexpresses one or more myomerger polypeptides, one or more myomaker polypeptides, or a combination thereof.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle is a pseudotyped exosome and the exosome producing cell is (a) a muscle cell that overexpresses one or more myomerger polypeptides, one or more myomaker polypeptides, or a combination thereof, (b) a myoblast that overexpresses one or more myomerger polypeptides, one or more myomaker polypeptides, or a combination thereof, (c) a myotube that overexpresses one or more myomerger polypeptides, one or more myomaker polypeptides, or a combination thereof, or (d) a fibroblast that expresses one or more myomerger polypeptides, one or more myomaker polypeptides, or a combination thereof.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomerger polypeptides is a wt-myomerger polypeptide.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomerger polypeptides comprises at least one amino acid modification relative to a wt-myomerger polypeptide.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomerger polypeptides comprises at least one amino acid modification relative to a wt-myomerger polypeptide and the at least one amino acid modification is an insertion, a deletion, or a substitution.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomerger polypeptides is selected from the group consisting of SEQ ID NO:
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomerger polypeptides is a human myomerger polypeptide.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomerger polypeptides is SEQ ID NO:19.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomerger polypeptides has at least an 80% sequence identity to a wt-myomerger polypeptide.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomerger polypeptides has at least a 90% sequence identity to a wt-myomerger polypeptide.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomerger polypeptides is an extracellular wt-myomerger polypeptide.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomerger polypeptides comprises (a) amino acids 4-15 of any of SEQ ID Nos:
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomerger polypeptides comprises (a) LLPLLRRLARRL (SEQ ID NO:41), (b) QDMREALLSCLLFVL (SEQ ID NO:42) or QDMREALLGCLLFIL (SEQ ID NO:43), or (c) both.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomerger polypeptides has at least an 80% sequence identity to an extracellular wt-myomerger polypeptide.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomerger polypeptides has at least a 90% sequence identity to an extracellular wt-myomerger polypeptide.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomaker polypeptides is a wt-myomaker polypeptide.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomaker polypeptides comprises at least one amino acid modification relative to a wt-myomaker polypeptide.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomaker polypeptides comprises at least one amino acid modification relative to a wt-myomaker polypeptide and the at least one amino acid modification is an insertion, a deletion, or a substitution.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomaker polypeptides is selected from the group consisting of SEQ ID NO:
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomaker polypeptides is a human myomerger polypeptide.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomaker polypeptides is SEQ ID NO:1.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomaker polypeptides has at least an 80% sequence identity to a wt-myomaker polypeptide.
The pseudotyped particle of any of the preceding claims, wherein at least one of the one or more myomaker polypeptides has at least a 90% sequence identity to a wt-myomaker polypeptide.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle comprises one or more myomaker polypeptides and one or more myomerger polypeptides.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle further comprises one or more nucleic acid molecules.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle does not comprise a myomerger nucleic acid molecule.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle does not comprise a myomaker nucleic acid molecule.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle does not comprise a myomerger nucleic acid molecule and does not comprise a myomaker nucleic acid molecule.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle further comprises a nucleic acid encoding a gene of interest.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle further comprises a nucleic acid encoding a gene of interest and the nucleic acid encoding the gene of interest does not encode for a myomaker polypeptide or a myomerger polypeptide.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle further comprises a nucleic acid encoding a gene of interest and the gene of interest is a therapeutic gene or a reporter gene.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle further comprises a nucleic acid encoding a gene of interest and the gene of interest is a gene for delivery to a muscle cell.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle further comprises a nucleic acid encoding a gene of interest and the gene of interest is a dystrophin nucleic acid molecule.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle further comprises a nucleic acid encoding a gene of interest and the gene of interest encodes a dystrophin polypeptide.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle further comprises a nucleic acid encoding a gene of interest and the gene of interest encodes a microdystrophin or a minidystrophin.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle further comprises a nucleic acid that can modulate gene expression.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle further comprises a nucleic acid that can modulate gene expression selected from a gRNA/Cas9 and an anti-sense oligonucleotide.
The pseudotyped particle of any of the preceding claims, wherein the pseudotyped particle exhibits fusogenic activity with a target cell upon binding of the myomaker polypeptide and/or a myomerger polypeptide to a myomaker polypeptide and/or myomerger polypeptide on the target cell.
A method for producing a pseudotyped lentivirus comprising
A method for producing a pseudotyped VSV comprising
A method of producing a pseudotyped exosome comprising (a) growing exosome producing cells that express at least one myomerger polypeptide, at least one myomaker polypeptide, a polypeptide of interest, or a combination thereof, (b) optionally contacting the exosome producing cells with a nucleic acid of interest, the polypeptide of interest, or a combination thereof, and (c) placing the exosome producing cells in an exosome depleted media.
A modified cell comprising one or more nucleic acids encoding proteins for pseudotyped particle production and nucleic acid encoding a myomaker polypeptide and/or a myomerger polypeptide.
A modified cell comprising a nucleic acid encoding a myomaker polypeptide and/or a myomerger polypeptide, wherein the nucleic acid encoding the myomaker polypeptide and/or the myomerger polypeptide is linked to an inducible response element, optionally a promoter.
Dependencies are inferred from the claim text.