Compositions useful for treatment of Charcot-Marie-Tooth disease

A recombinant adeno-associated virus (rAAV) comprising an AAV capsid and packaged therein a vector genome, wherein the vector genome comprises:

• (a) an AAV 5′ inverted terminal repeat (ITR);
• (b) an CB7.CI.hMfn2.GA.link.miR538.rBG expression cassette comprising at least one open reading frame (ORF) comprising (i) an engineered nucleic acid sequence of SEQ ID NO:
• 11 or a sequence at least 90% identical thereto encoding a human mitofusin 2 (hMfn2), (ii) a spacer sequence located between (i) and (iii), and (iii) at least one miRNA coding sequence which is specific for a target site in an endogenous human mitofusin 2 nucleic acid sequence in a patient having a disorder associated with deficient hMfn2, wherein at the at least one miRNA comprises miR538,
• wherein the engineered nucleic acid sequence of (i) lacks the target site for the at least one miRNA of (iii), thereby preventing the at least one miRNA from targeting the engineered hMfn2 coding sequence;
• wherein the regulatory control sequences comprise a cytomegalovirus immediate early (CMV IE) enhancer and a chicken beta actin (CB) promoter, and further comprising a chicken beta-actin intron (CI), and a rabbit beta globin (rBG) polyadenylation (polyA) signal;
• and
• (c) an AAV 3′ ITR.