Polynucleotides Encoding Acyl-CoA Dehydrogenase, Very Long-Chain for the Treatment of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency

摘要

The invention relates to mRNA therapy for the treatment of VLCADD. mRNAs for use in the invention, when administered in vivo, encode human acyl-CoA dehydrogenase, very longchain (ACADVL), isoforms thereof, functional fragments thereof, and fusion proteins comprising ACADVL. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of ACADVL expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient ACADVL activity in subjects, namely acylcarnitine and acylcarnitine metabolites.