The present disclosure provides high-performance hybridization reagents for use in a variety of hybridization assays and other related techniques. The hybridization reagents comprise an oligonucleotide probe and a bridging antigen, wherein the bridging antigen is recognized by a detectable antibody with high affinity. Also provided are compositions comprising panels of hybridization reagents specific for multiple different target nucleic acids and compositions comprising pairs of hybridization reagents and their complementary detectable antibodies. The paired hybridization reagents and detectable antibodies are useful in a variety of hybridization assays, particularly in highly multiplexed assays, where the structure of the bridging antigen is varied in tandem with variation in the detectable antibody, such that a multiplicity of hybridization reagents are provided that are capable of simultaneously detecting a multiplicity of target nucleic acids in a single assay. Also provided are kits comprising the hybri