The major goal of this project is to produce antisense-oligodeoxynucleotides that will readily be taken up by target cells. To accomplish this, Reliable Chemical Company proposes to attach antibiotics to antisense-oligodeoxyncleotides utilizing novel technologies. The antibiotics to be employed are readily taken up by eukaryotic cells and should act as permeation enhancers for the oligodeoxynucleotides. Antibiotics have been chosen, because in addition to theiruptake by cells, they are FDA approved drugs; safe for use in humans. They arenot readily metabolized by eukaryotes and thus should form stable conjugates. The criteria for successful conjugates will be inhibition of protein synthesis of target mRNA, increased uptake into cells, and relative ease of synthesis. If thesecriteria are met, antibiotic-oligodeoxynucleotide conjugates will have great potential in the antisense oligodeoxynucleotide field of drug therapy, especially in the area of antiviral drugs. One of the major problems facing this area today is the efficient uptake of antisense oligodeotides into eukaryotic cells. The proposed conjugates should minimize this situation. The proposed innovative technology developed from this project will be applicable to the attachment of other types of molecules to antisense oligodeoxynucleotides.