Abstract: Methods for modifying a dystrophin gene are disclosed, for restoring dystrophin expression within a cell having an endogenous frameshift or nonsense mutation within the dystrophin gene. The methods comprise introducing a first cut within an exon en or intron of the dystrophin gene creating a first exon end or intron end, wherein said first cut is located upstream of the endogenous frameshift or nonsense mutation; and introducing a second cut within an exon or intron of the dystrophin gene creating a second exon end or intron end, wherein said second cut is located downstream of the frameshift or nonsense mutation. Upon joining/ligation of said first and second exon ends or intron ends a hybrid exon or intron junction is created and dystrophin expression is restored, as the correct reading frame is restored. Reagents and uses of the method are also disclosed, for example to treat a subject suffering from muscular dystrophy.

Abstract: Methods of modifying a dystrophin gene are disclosed, for restoring dystrophin expression within a cell having an endogenous frameshift mutation within the dystrophin gene. The methods comprising introducing a first cut within an exon of the dystrophin gene creating a first exon end, wherein said first cut is located upstream of the endogenous frameshift mutation; and introducing a second cut within an exon of the dystrophin gene creating a second exon end, wherein said second cut is located downstream of the frameshift mutation. Upon joining/ligation of said first and second exon ends dystrophin expression is restored, as the correct reading frame is restored. Reagents and uses of the method are also disclosed, for example to treat a subject suffering from muscular dystrophy.