Abstract: A polynucleotide encoding a thymidine kinase wherein the thymidine kinase coding region does not contain a functional splice acceptor and/or splice donor site. An expression vector comprising said polynucleotide. The polynucleotides and expression vectors are useful in gene therapy. The polynucleotides and vectors are useful in destroying cells when used in conjunction with a substantially non-toxic agent, such as ganciclovir, which is converted by thymidine kinase to a toxic agent.