Extended Data Fig. 1: Evolution of dystrophin and utrophin and the framework for therapeutic vector design.
From: Non-immunogenic utrophin gene therapy for the treatment of muscular dystrophy animal models
a, Reconstructed timeline of the dystrophin/utrophin divergence illustrating the timing of two independent duplications and three subsequent lineage-specific deletions (&, @, $, %, #). The timing of the dystrophin/utrophin duplication correlates with the emergence of hinged jaws, oligodendrocytes and membrane in-folding at the neuromuscular junctional site where utrophin is most highly expressed. MYA, million years ago. b, Delineation of domain conservation relative to recombinant proteins compatible with the size limit for AAV transgenes, including dystrophin-based constructs in early-stage clinical investigation and others described in the text. ClinicalTrials.gov reference numbers: *NCT03362502, ~NCT02376816 and ^NCT03368742. Symbols (@, $, %, #) indicate the positions of naturally occurring lineage-specific deletions; localization of epitopes recognized by anti-utrophin antibodies Utro N and C are depicted at the extreme lower edge of the figure.
