The present invention provides methods and compositions for highly
sensitive nucleic acid detection, down to the single nucleic acid
molecule level. In one aspect, the present invention provides methods for
detecting a target nucleic acid comprising: (a) providing first and
second target-specific nucleic acids, wherein the first and second
target-specific nucleic acids each comprise sequences complementary to
the target nucleic acid; wherein the first target specific nucleic acid
is bound to a first affinity tag and the second target-specific nucleic
acid is bound to a second affinity tag, wherein the first affinity tag is
capable of binding to a molecular motor, and wherein the second affinity
tag is capable of binding to a detection probe; (b) contacting the first
and second target-specific nucleic acids to a sample under conditions
whereby the first and second target-specific nucleic acids will hybridize
to the target nucleic acid if the target nucleic acid is present in the
sample, wherein upon hybridization to the target nucleic acid the first
and second target-specific nucleic acids are directly adjacent to each
other; (c) ligating the first and second target-specific nucleic acids
together; (d) binding the molecular motor t.about. the first affinity tag
and the detection probe to the second affinity tag; (e) inducing movement
of the molecular motor; and (f) detecting movement of the molecular motor
through the detection probe, wherein the movement of the molecular motor
serves to detect the target nucleic acid in the sample.