MRNA therapy for argininosuccinate synthetase deficiency
AssigneeTranslate Bio, Inc.
InventorsMichael Heartlein, Frank DeRosa, Lianne Smith
Life of this patent
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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.
Claims16
A method of treating Argininosuccinate Synthetase Deficiency (ASD), the method comprising
- administering intravenously to a subject with the ASD a composition comprising an mRNA-loaded liposome at an effective dose and administration interval to treat the ASD;
- wherein the administering results in reduced ammonia levels in a blood sample from the treated subject as compared to a baseline ammonia level before treatment;
- wherein the mRNA encodes an human argininosuccinate synthetase (ASS1) and comprises a nucleotide sequence at least 90% identical to
- SEQ ID NO:
- 3
- AUGAGCAGCAAGGGCAGCGUGGUGCUGGCCUACAGCGGCGGCCUGGACACC
- AGCUGCAUCCUGGUGUGGCUGAAGGAGCAGGGCUACGACGUGAUCGCCUAC
- CUGGCCAACAUCGGCCAGAAGGAGGACUUCGAGGAGGCCCGCAAGAAGGCC
- CUGAAGCUGGGCGCCAAGAAGGUGUUCAUCGAGGACGUGAGCCGCGAGUUC
- GUGGAGGAGUUCAUCUGGCCCGCCAUCCAGAGCAGCGCCCUGUACGAGGAC
- CGCUACCUGCUGGGCACCAGCCUGGCCCGCCCCUGCAUCGCCCGCAAGCAG
- GUGGAGAUCGCCCAGCGCGAGGGCGCCAAGUACGUGAGCCACGGCGCCACC
- GGCAAGGGCAACGACCAGGUGCGCUUCGAGCUGAGCUGCUACAGCCUGGCC
- CCCCAGAUCAAGGUGAUCGCCCCCUGGCGCAUGCCCGAGUUCUACAACCGC
- UUCAAGGGCCGCAACGACCUGAUGGAGUACGCCAAGCAGCACGGCAUCCCC
- AUCCCCGUGACCCCCAAGAACCCCUGGAGCAUGGACGAGAACCUGAUGCAC
- AUCAGCUACGAGGCCGGCAUCCUGGAGAACCCCAAGAACCAGGCCCCCCCC
- GGCCUGUACACCAAGACCCAGGACCCCGCCAAGGCCCCCAACACCCCCGAC
- AUCCUGGAGAUCGAGUUCAAGAAGGGCGUGCCCGUGAAGGUGACCAACGUG
- AAGGACGGCACCACCCACCAGACCAGCCUGGAGCUGUUCAUGUACCUGAAC
- GAGGUGGCCGGCAAGCACGGCGUGGGCCGCAUCGACAUCGUGGAGAACCGC
- UUCAUCGGCAUGAAGAGCCGCGGCAUCUACGAGACCCCCGCCGGCACCAUC
- CUGUACCACGCCCACCUGGACAUCGAGGCCUUCACCAUGGACCGCGAGGUG
- CGCAAGAUCAAGCAGGGCCUGGGCCUGAAGUUCGCCGAGCUGGUGUACACC
- GGCUUCUGGCACAGCCCCGAGUGCGAGUUCGUGCGCCACUGCAUCGCCAAG
- AGCCAGGAGCGCGUGGAGGGCAAGGUGCAGGUGAGCGUGCUGAAGGGCCAG
- GUGUACAUCCUGGGCCGCGAGAGCCCCCUGAGCCUGUACAACGAGGAGCUG
- GUGAGCAUGAACGUGCAGGGCGACUACGAGCCCACCGACGCCACCGGCUUC
- AUCAACAUCAACAGCCUGCGCCUGAAGGAGUACCACCGCCUGCAGAGCAAG
- GUGACCGCCAAGUGA;
- wherein the liposome has a diameter less than about 100 nm;
- 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 method of treating Argininosuccinate Synthetase Deficiency (ASD), the method comprising
- administering intravenously to a subject with the ASD a composition comprising an mRNA molecule encoding an human argininosuccinate synthetase (ASS1) encapsulated in a liposome at an effective dose and an administration interval such that the administering of the composition results in reduced ammonia levels in a blood sample from the treated subject as compared to a baseline ammonia level before treatment,
- wherein the liposome has a diameter of less than about 100 nm, and
- wherein the liposome comprises cKK-E12:
Dependencies are inferred from the claim text.