Abstract: The invention concerns a polypeptide having a uracil phosphoribosyl transferase (UPRTase) activity derived from a native UPRTase by mutation of one or several residues of said UPRTase. The invention also concerns a nucleotide sequence coding for said UPRTase mutant, a vector for expressing the latter, a viral particle and a host cell as well as a composition containing them. The invention further concerns their therapeutic use and a treatment method using them. The invention is particularly useful in the context of therapy by suicide genes in particular for treating proliferative and infectious diseases.