MRNA therapy for argininosuccinate synthetase deficiency
AssigneeTranslate Bio, Inc.
InventorsMichael Heartlein, Frank DeRosa, Lianne Boeglin
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Abstract
The present invention provides, among other things, methods of treating Argininosuccinate Synthetase Deficiency (ASD), including administering to a subject in need of treatment a composition comprising an mRNA encoding argininosuccinate synthetase (ASS1) at an effective dose and an administration interval such that at least one symptom or feature of ASD is reduced in intensity, severity, or frequency or has delayed in onset. In some embodiments, the mRNA is encapsulated in a liposome comprising one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids.
Claims32
A composition for treating Argininosuccinate Synthetase Deficiency (ASD), comprising an mRNA encoding argininosuccinate synthetase (ASS1) at an effective dose encapsulated within a liposome, wherein the mRNA encodes an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO:2, wherein the mRNA further comprises a 5′ untranslated region (UTR), wherein the 5′ UTR comprises the nucleic acid sequence of SEQ ID NO:4, and wherein the liposome comprises one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids, and one or more poly(ethylene) (PEG)-modified lipids.
A composition for treating ASD, comprising an mRNA encoding ASS1 at an effective dose encapsulated within a liposome, wherein the mRNA encodes an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO:2, wherein the mRNA further comprises a 3′ UTR, wherein the 3′ UTR comprises the nucleic acid sequence of SEQ ID NO:5, and wherein the liposome comprises one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids, and one or more PEG-modified lipids.
A composition for treating ASD, comprising an mRNA encoding ASS1 at an effective dose encapsulated within a liposome, wherein the mRNA comprises a nucleic acid sequence that is at least 90% identical to the nucleic acid sequence of SEQ ID NO:
- 13, and wherein the liposome comprises one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids, and one or more PEG-modified lipids.
A composition for treating ASD, comprising an mRNA encoding ASS1 at an effective dose encapsulated within a liposome, wherein the mRNA encodes an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO:2, wherein the mRNA further comprises a 3′ UTR, wherein the 3′ UTR comprises the nucleic acid sequence of SEQ ID NO:6, and wherein the liposome comprises one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids, and one or more PEG-modified lipids.
A composition for treating ASD, comprising an mRNA encoding ASS1 at an effective dose encapsulated within a liposome, wherein the mRNA comprises a nucleic acid sequence that is at least 90% identical to the nucleic acid sequence of SEQ ID NO:
- 14, and wherein the liposome comprises one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids, and one or more PEG-modified lipids.
A composition for treating ASD, comprising an mRNA encoding ASS1 at an effective dose encapsulated within a liposome, wherein the mRNA comprises a nucleic acid sequence that is at least 90% identical to the nucleic acid sequence of SEQ ID NO:
- 15, and wherein the liposome comprises one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids, and one or more PEG-modified lipids.
Dependencies are inferred from the claim text.