Modifications for antisense compounds

A method of detecting a target oligonucleotide in a sample, the method comprising:

• (a) contacting the sample with a composition comprising a probe oligonucleotide capable of hybridizing with the target oligonucleotide, the probe oligonucleotide having the structure 5′-Y1—X—Y2-3′, wherein
• Y1 comprises a fluorophore at or near the 5′-terminus of the probe oligonucleotide and a sequence of 8-12 DNA or RNA nucleotides comprising a nucleotide N1 having a 3′ phosphate covalently linked to X;
• Y2 comprises a quencher located at or near the 3′-terminus of the probe oligonucleotide and a sequence of DNA or RNA nucleotides comprising a nucleotide N2 having a 5′ phosphate covalently linked to X;
• and
• X comprises an internal quencher;
• wherein fluorescence of the fluorophore is reduced when the probe oligonucleotide is not hybridized to the target oligonucleotide;
• and
• (b) detecting the presence of the target oligonucleotide in the sample when an increase in fluorescence of the composition is detected as compared to the fluorescence of the composition in a control sample devoid of the target oligonucleotide.