MITOCHONDRIAL TARGETING AND THERAPEUTIC USE THEREOF

摘要

The present invention provides, among other things, compositions and methods for treatment of Friedrich's Ataxia based on effective targeting of a therapeutic moiety to mitochondria that can substitute for natural FXN protein activity or rescue one or more phenotypes or symptoms associated with frataxin-deficiency. In some embodiments, the present invention provides a targeted therapeutic comprising a therapeutic moiety, which is a polypeptide having an N-terminus and a C-terminus, a mitochondrial targeting sequence associated with the therapeutic moiety at the N-terminus, and a mitochondrial membrane-penetrating peptide associated with the therapeutic moiety at the C-terminus, wherein the therapeutic moiety is targeted to mitochondria upon cellular entry.

主权项

1. A targeted therapeutic comprising
a therapeutic moiety, which is a polypeptide having an N-terminus and a C-terminus and an amino acid sequence at least 80% identical to mature human Frataxin protein (SEQ ID N0:1); a mitochondrial targeting sequence; and a mitochondrial membrane-penetrating peptide, wherein the mitochondrial targeting sequence is associated with the N-terminus of the therapeutic moiety and the mitochondrial membrane-penetrating peptide is associated with the C-terminus of the therapeutic moiety, and further wherein the therapeutic moiety is targeted to mitochondrial upon cellular entry.