Methods for treatment of methylmalonic acidemia
AssigneeTranslate Bio, Inc.
InventorsLianne Boeglin, Christian Cobaugh, Frank DeRosa, Michael Heartlein, Kim Askew
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Abstract
The present invention provides, among other things, methods and compositions for treating methylmalonic academia (MMA) based on mRNA therapy. The compositions used in treatment of MMA comprise an mRNA comprising a methymalonyl-CoA mutase (MUT) coding sequence and are administered at an effective dose and an administration interval such that at least one symptom or feature of MMA is reduced in intensity, severity, or frequency or has a delayed onset. mRNAs with optimized MUT coding sequences are provided that can be administered without the need for modifying the nucleotides of the mRNA to achieve sustained in vivo function.
Claims14
A method of treating methylmalonic acidemia (MMA) in a subject in need thereof, the method comprising intravenously administering to the subject a composition comprising an mRNA comprising a codon-optimized methylmalonyl-CoA mutase (MUT) coding sequence,
- wherein the mRNA is administered such that MUT expression is detected in the liver,
- wherein the mRNA is encapsulated within a liposome that 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,
- wherein the nucleotides of the mRNA are unmodified,
- wherein the codon-optimized MUT coding sequence comprises the nucleotide sequence as set forth in SEQ ID NO:
- 4, and
- wherein the mRNA comprises a 3′ poly(A) tail sequence that is 300-800 nucleotides long, thereby treating MMA in the subject.
A method of treating methylmalonic acidemia (MMA) in a subject in need thereof, the method comprising intravenously administering to the subject a composition comprising an mRNA comprising a codon-optimized methylmalonyl-CoA mutase (MUT) coding sequence,
- wherein the mRNA is administered such that MUT expression is detected in the liver,
- wherein the mRNA is encapsulated within a liposome that 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,
- wherein the nucleotides of the mRNA are unmodified,
- wherein the codon-optimized MUT coding sequence comprises the nucleotide sequence as set forth in SEQ ID NO:
- 5, and
- wherein the mRNA comprises a 3′ poly(A) tail that is 300-800 nucleotides long, thereby treating MMA in the subject.
Dependencies are inferred from the claim text.