Use of meganucleases for inducing homologous recombination ex vivo and in toto in vertebrate somatic tissues and application thereof

A single chain homing endonuclease, comprising a first variant of I-CreI having the amino acid sequence of accession number pdb 1g9y and a second variant of I-CreI variant having the amino acid sequence of accession number pdb 1g9y in a single polypeptide, wherein

• said first variant of I-CreI contains one to six substitutions in the sequence of amino acid residues 26 to 40 and one to three substitutions in the sequence of amino acid residues 44 to 77, wherein in said first variant of I-CreI there is a substitution at least at positions 33 and 68, and
• independently, said second variant of I-CreI contains one to six substitutions in the sequence of amino acid residues 26 to 40 and one to three substitutions in the sequence of amino acid residues 44 to 77, wherein in said second variant of I-CreI there is a substitution at least at positions 26, 30, 32, 38, 44, and 68.