Using Human Observations To Gain Biologic Insights And New Treatments; Discovery Of A Quadruplex-Forming Dna Aptamer As An Anticancer Agent

The discovery and characterization of the primo vascular system represents a major new development in our understanding of human biology. The current understanding of this novel system is based on careful observations over an extended period of time. We have, in an analogous fashion, used clinical observations in patients with malignant diseases to develop new insights which have led to novel types of therapies. Beginning with the observation, in 1979, of in vivo differentiation of chronic myelogenous leukemia cells in a patient treated with the RNA synthesis inhibitor, mithramycin, we have characterized the ability of DNA binding compounds to inhibit gene expression. As a result of this work, we have discovered a quadruplex-forming, DNA aptamer, AS1411, which has significant anticancer activity with very little toxicity. AS1411 is currently in Phase IIb studies. We have recently shown that genomic quadruplex-forming sequences are selectively toxic to transformed cells and have therapeutic potential.