DESIGN AND APPLICATION OF ANTISENSE OLIGONUCLEOTIDES IN CELL-CULTURE,IN-VIVO, AND AS THERAPEUTIC AGENTS

1. Synthetic oligonucleotides can inhibit the expression of a gene in a sequence specific manner on the transcriptional and translational le vel, These molecules are usually referred to as antisense oligonucleot ides. 2. Antisense mediated inhibition of gene expression is a valuabl e tool to analyze the function of a gene in vivo and can also be used for therapeutic gene suppression. 3. A number of factors such as the m ode of action, specificity, chemistry, and pharmacology must be carefu lly considered for the design and successful application of antisense oligonucleotides. 4. Assay systems and controls must be chosen as to a ssure that the observed biological effects of antisense oligonucleotid es do in fact reflect the result of a specific gene inhibition, 5. Thi s article critically discusses these factors in view of the literature and our own experience with a wide range of cell types and animal mod els, targeting different genes, The emphasis is on the use of phosphor othioate oligodeoxynucleotides in cell cultures, in vivo, and as poten tial drugs.