Abstract: Novel antisense oligonucleotides are disclosed. The present oligonucleotides have increased resistance to nuclease attack and manifest increased efficacy in combating pathogenic infections. The present oligonucleotides comprise two or more identical or different sequences, each complementary to a nucleic acid sequence of a pathogen that is essential to the pathogen's metabolism and/or reproduction. The sequences may be complementary to the same or different target nucleic acid sequence within a single pathogen, to target sequences on different strains of the same pathogen, or to target sequences on different pathogens. In the preferred embodiment, the sequences are coupled via a 3′-3′ linkage, which greatly reduces 3′ nucleolytic degradation.