Abstract: Methods, reagents and compositions for providing more accurate and reliable genetic modification are provided. In particular, a nucleic acid encoding a fusion protein comprising a 5? to 3? DNA exonuclease domain and an RNA binding domain is described. Also provided are methods, reagents and compositions for in vivo genetic modification of the genome of a human or animal cell. Furthermore, the present application relates to uses of the said methods, reagents and compositions in the treatment of disease and production of transgenic animals.

Abstract: Methods, reagents and compositions for providing more accurate and reliable genetic modification are provided. In particular a nucleic acid encoding a fusion protein comprising an endonuclease domain and a binding domain for an origin of replication is described. Also provided are methods, reagents and compositions for in vivo genetic modification of the genome of a non-animal cell or organism. Furthermore, the present application relates to uses of the said methods, reagents and compositions for introducing desirable traits to non-animal organisms or ameliorating or removing non-desirable traits in these organisms including in the treatment of disease.