Gene therapy Alan M Gewirtz
Signiﬁcant progress is being made in the identiﬁcation of genes responsible for cell growth and malignant transformation.1-3 With this knowledge has come a natural desire to ‘translate’ this information into new, ‘target-speciﬁc’, therapeutic strategies for the treatment of cancer. The recent development of a relatively speciﬁc biochemical inhibitor of the BCR/ABL protein tyrosine kinase in patients with chronic myeloid leukemia (CML)4 is a stunning example of this quest (see Chapters 32 and 34). For therapies aimed directly at replacement, repair, or disabling of disease-causing genes, progress has been slower, and a success equivalent to the biochemical BCR/ABL inhibitor has yet to be achieved. The reasons for this are complex, and vary with the type of gene-directed therapy being employed. For strategies involving the use of viral vectors, issues related to efﬁcient infection of human hematopoietic stem cells, as well as efﬁciency and persistence of expression of the gene cassette transferred, remain unsolved problems. The ‘simpler’ approach of delivering a gene-modifying nucleic acid, such as an antisense oligodeoxynucleotide or ribozyme, has also proven problematic. There are many recent reviews discussing the problems and potential of these various
approaches.5-7 This chapter will focus on the use of nucleic acid molecules, the so-called ‘antisense’ strategy, for treating CML, and will brieﬂy discuss approaches employing viral vectors.