Nucleic Acid Therapeutics for Human Leukemia: Development and Early Clinical Experience with Oligodeoxynucleotides Directed at c-myb

For the past several years, we have been engaged in trying to develop an effective strategy of disrupting specific gene function with antisense oligodeoxynucleotides (ODN). We have also been actively engaged in attempting to utilize this strategy in the clinic. This latter pursuit has focused on finding appropriate gene targets that can be successfully targeted using an antisense approach and then developing “scale-up” methods so that techniques developed in the laboratory can be applied in the clinic. It was our opinion that human leukemias would be particularly amenable to this therapeutic strategy. They can be successfully manipulated ex vivo, the tumor is “liquid” in vivo and therefore more likely to successfully take up ODN, and a great deal is known about their cell and molecular biology. The latter in particular facilitates the choice of a gene target. Accordingly, if ODN were going to be developed as therapeutics, the hematopoietic system seemed an ideal model system.