This patent application relates to hybrid and/or single-chain rare-cuttingendonucleases, called meganucleases, which recognize and cleave a specificnucleotide sequence, to polynucleotide sequences encoding for said rare-cutting endonucleases, to a vector comprising one of said polynucleotidesequences, to a cell or animal non-human comprising one of said polynucleotidesequences or said rare-cutting endonucleases, to a process for producing oneof said rare-cutting endonucleases and any use of the disclosed products andmethods. More particularly, this invention contemplates any use of such rare-cutting endonuclease for genetic engineering and gene therapy.