THERAPEUTIC OLIGONUCLEOTIDES OF REDUCED TOXICITY

摘要

It has now been discovered that oligonucleotides which tend to form multimer ic aggregates have greater toxicity in the aggregate form than in monomeric for m. Thus, the present invention provides therapeutic oligonucleotide composition s of reduced in vivo toxicity, and a method for making such compositions, as well as a method for administration of the therapeutic oligonucleotide, wher e the therapeutic oligonucleotide in one that tends to form multimeric aggregates. Compositions containing such aggregate-forming oligonucleotides are treated by heating, preferably no more than 24 hours prior to administration, or using chemical species such as mannitol which disrupt aggregates.