MODIFIED POLYNUCLEOTIDES FOR TREATING LIPASE A, LYSOSOMAL ACID, CHOLESTEROL ESTERASE PROTEIN DEFICIENCY

摘要

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

主权项

1. A method of producing a polypeptide of interest in a mammalian cell or tissue comprising contacting said mammalian cell or tissue with a modified mRNA, wherein said modified mRNA encodes a member selected from the group consisting of lipase A, lysosomal acid, cholesterol esterase (SEQ ID NO: 1127), lipase A, lysosomal acid, cholesterol esterase (SEQ ID NO: 1128), lipase A, lysosomal acid, cholesterol esterase (SEQ ID NO: 1129), lipase A, lysosomal acid, cholesterol esterase (SEQ ID NO: 1130), lipase A, lysosomal acid, cholesterol esterase (SEQ ID NO: 1131), lipase A, lysosomal acid, cholesterol esterase (SEQ ID NO: 1132), lipase A, lysosomal acid, cholesterol esterase (SEQ ID NO: 1133), lipase A, lysosomal acid, cholesterol esterase (SEQ ID NO: 1134), lipase A, lysosomal acid, cholesterol esterase (SEQ ID NO: 1135), lipase A, lysosomal acid, cholesterol esterase (SEQ ID NO: 1136) and lipase A, lysosomal acid, cholesterol esterase (SEQ ID NO: 1137), and wherein said modified mRNA comprises modifications selected from the group consisting of:
(a) 5-methylcytosine and 2-thiouridine, (b) pseudouridine and 5-methylcytosine, and (c) 1-methylpseudouridine.