With the impending availability of total information about nucleic acid seq
uences in humans and other organisms, tools to investigate these sequences
on a large scale assume increasing importance. Methods currently in use, ho
wever, cannot offer the required combination of high-throughput, sensitivit
y and specificity of detection. Padlock probes, circularizing oligonucleoti
des, may provide a means to detect, distinguish, quantitate and also locate
very large numbers of DNA or RNA sequences. Recent developments in areas s
uch as the biochemistry of ligation and characterization of ligases, method
s to replicate circularized probes and the development of assays based on t
hese principles augment the potential of padlock probes.