Compositions and methods of altering cholesterol levels

摘要

The present invention relates to compositions, methods and kits using polynucleotides, primary transcripts and mmRNA molecules.

主权项

1. A method of reducing serum levels of cholesterol in a subject comprising administering to said subject a modified mRNA encoding a LDLR mutant, said modified mRNA comprising at least one nucleoside modification, wherein said at least one nucleoside modification is 1-methylpseudouridine and wherein said modified mRNA encodes a protein identical to SEQ ID NO: 19 except for one or more substitution mutations that change the identity of one or more amino acids at one or more of positions 316-339 of SEQ ID NO: 19 in combination with an mRNA encoding a CYP7A1 protein, said mRNA comprising the base sequence of SEQ ID NO: 39 except that each thymidine is replaced by a uridine.