Meganuclease variants which cleave at least one target in the provirus of a retrovirus and in particular which cleave the genomic insertion of the provirus. The present invention in particular relates to meganuclease variants which cleave the provirus of the Human Immunodeficiency Virus genome following genomic insertion. Vector encoding such variants, as well as to a cell or multi-cellular organism modified by such a vector and use of said meganuclease variants and derived products for genome engineering and for in vivo and ex vivo (gene cell therapy) genome therapy.
