ANTISENSE APPROACHES TO THE GENE-THERAPY OF CANCER - RECNAC

This review has looked at the wide-ranging research initiatives in the field of antisense technology. It starts with the philosophy behind a ntisense DNA and the production of antisense RNA from genetic construc ts and raises the various problems which are being addressed. These in clude uptake into cells, targeting the substrate sequence and cells, t he stability of the antisense molecules and pharmokinetic consideratio ns within animals. The review talks of the positive results attained i n vitro and in vivo in animal and plant experiments but also addresses the problems many workers have faced in the field. It attempts to res olve these differences in terms of the need for further understanding of the mechanisms by which the positive results have been obtained. Th e novel use of catalytic ribozymes (RNA) in downregulating genes is al so discussed in similar terms to antisense DNA and RNA. By taking a ca se study with a human leukaemia the review delves into the mysteries o f how different results can be resolved by improving the design of rib ozymes thereby increasing specificity and preventing aberrant reaction s. It is concluded that despite a lack of understanding of how the bio logical effects have come about in vitro and in vivo the clinical and research developments should resolve the issue of antisense potential for rational drug development.