Polynucleotides encoding branched-chain alpha-ketoacid dehydrogenase complex E1-α, E1-β, and E2 subunits for the treatment of maple syrup urine disease
AssigneeModernaTX, Inc.
InventorsPaolo G. V. Martini, Vladimir Presnyak, Paloma Hoban Giangrande, Kimberly Ann Coughlan
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Abstract
This disclosure relates to mRNA therapy for the treatment of maple syrup urine disease (MSUD). mRNAs for use in the invention, when administered in vivo, encode branched chain α-ketoacid dehydrogenase complex (BCKDC) E1α, E1β, or E2mRNA therapies of the disclosure increase and/or restore deficient levels of E1α, E1β, or E2 expression and/or BCKDC activity in subjects. mRNA therapies of the invention further decrease abnormal accumulation of branched chain amino acids associated with deficient BCKDC activity in subjects.
Claims9
A pharmaceutical composition comprising a lipid nanoparticle, a first mRNA, a second mRNA, and a third mRNA, wherein the first mRNA comprises a first open reading frame (ORF) encoding a branched-chain α-ketoacid dehydrogenase complex (BCKDC) Ela polypeptide comprising the amino acid sequence set forth in SEQ ID NO:
- 1 or 19, wherein the second mRNA comprises a second ORF encoding a BCKDC E1β polypeptide comprising the amino acid sequence set forth in SEQ ID NO:9, wherein the third mRNA comprises a third ORF encoding a BCKDC E2 polypeptide comprising the amino acid sequence set forth in SEQ ID NO:14, and wherein all of the uracils in the first mRNA, the second mRNA, and the third mRNA are N1-methylpseudouracils.
Dependencies are inferred from the claim text.