The invention relates to the use of gene therapy in the treatment of aseptic loosening of orthopaedic prostheses and discloses methods of refixing such prostheses without open revision surgery. In particular, it provides prodrugs and adenoviral vectors comprising genes encoding prodrugs converting enzymes for simultaneous, separate or sequential use in the destruction of interface tissue allowing subsequent recementing of loose prostheses in a minimally invasive manner.