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 antisense DNA and the production of antisense RNA from genetic constructs and raises the various problems which are being addressed. These include uptake into cells, targeting the substrate sequence and cells, the stability of the antisense molecules and pharmokinetic considerations within animals. The review talks of the positive results attained in vitro and in vivo in animal and plant experiments but also addresses the problems many workers have faced in the field. It attempts to resolve these differences in terms of the need for further understanding of the mechanisms by which the positive results have been obtained. The novel use of catalytic ribozymes (RNA) in downregulating genes is also discussed in similar terms to antisense DNA and RNA. By taking a case study with a human leukaemia the review delves into the mysteries of how different results can be resolved by improving the design of ribozymes thereby increasing specificity and preventing aberrant reactions. It is concluded that despite a lack of understanding of how the biological 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.
Gibson
I
I
School of Biological Sciences, University of East Anglia, Norwich, UK.
D001483:Base Sequence; D004247:DNA / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000627:therapeutic use*
D016376:Oligonucleotides, Antisense; D004247:DNA