The invention concerns a polypeptide having a uracil phosphoribosyl transferase (UPRTase) by mutation of one or several residues of the UPRTase. The invention also concerns a nucleotide sequence coding for the UPRTase mutant, a vector for expressing the latter, a viral particle, a host cell, and 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.