Non-invasive method for detecting target-RNA

A method of detecting in a subject, the occurrence of base-specific intracellular binding events involving a plurality of target RNAs, comprising

• (a) administering to the subject a plurality of different-sequence oligomeric antisense compounds, each having (i) from 8 to 40 bases, including a targeting base sequence that is complementary to a portion of an RNA transcript produced by a selected one of a plurality of target genes, (ii) a Tm, with respect to binding to a complementary RNA sequence, of greater than about 50° C., and (iii) an ability to be actively taken up by mammalian cells, and (iv) conferring resistance of complementary RNA hybridized with the agent to RNaseH,
• (b) at a selected time after said administering, taking a sample of a body fluid from the subject, and
• (c) detecting in the sample the presence of a nuclease-resistant heteroduplexes, each composed of the antisense oligomer and the complementary portion of the corresponding RNA transcript.

An diagnostic array device for use in a subject, the occurrence of base-specific intracellular binding events involving a plurality of target RNAs, comprising

• a substrate divided into a plurality of regions, and
• (d) carried on each array region, a sequence-specific binding agent capable of binding to a specific-sequence heteroduplex composed of an RNA oligomer of a specific sequence and a complementary-sequence antisense oligomer characterized by (i) a Tm, with respect to binding to the complementary RNA oligomer, of greater than about 50° C., and (iii) an ability to be actively taken up by mammalian cells, and (iv) conferring resistance of complementary RNA hybridized with the agent to RNaseH,
• where each of said binding agents is selected from the group consisting of (a) an antibody capable of binding in a sequence-dependent manner to a heteroduplex in a sequence-dependent manner, (b) an antibody capable of binding to a sequence-specific antigen attached to the antisense compound, and (c) a sequence-specific duplex-binding oligomer.

A monoclonal antibody having specific binding affinity for a heteroduplex composed of an RNA oligomer and a complementary-sequence antisense oligomer characterized by (i) a substantially uncharged backbone, (ii) a Tm, with respect to binding to the complementary RNA oligomer, of greater than about 50° C., and (iii) an ability to be actively taken up by mammalian cells, and (iv) conferring resistance of complementary RNA hybridized with the agent to RnaseH.