Polynucleotides encoding lipoprotein lipase for the treatment of hyperlipidemia

A pharmaceutical composition comprising a lipid nanoparticle, wherein the lipid nanoparticle comprises a compound having the Formula (IA)

• or a salt or stereoisomer thereof, wherein
• l is selected from 1, 2, 3, 4, and 5;
• m is selected from 5, 6, 7, 8, and 9;
• M1 is a bond or M′;
• R4 is unsubstituted C1-3 alkyl, or —(CH2)nQ, wherein n is 1, 2, 3, 4, or 5 and Q is OH, —NHC(S)N(R)2, or —NHC(O)N(R)2;
• M and M′ are independently selected from —C(O)O—, —OC(O)—, —C(O)N(R′)—, —OP(O)(OR′)O—, an aryl group, and a heteroaryl group;
• R2 and R3 are independently selected from the group consisting of H, C1-14 alkyl, and C2-14 alkenyl;
• each R is independently selected from the group consisting of C1-3 alkyl, C2-3 alkenyl, and H;
• each R′ is independently selected from the group consisting of C1-18 alkyl, C2-18 alkenyl, —R*YR″, —YR″, and H;
• each R″ is independently selected from the group consisting of C3-14 alkyl and C3-14 alkenyl;
• each R* is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl;
• and
• each Y is independently a C3-6 carbocycle;
• wherein the lipid nanoparticle comprises an mRNA that comprises an open reading frame (ORF) encoding a lipoprotein lipase (LPL) polypeptide.