Signal activated RNA interference

A signal-activatable polynucleotide construct for enzyme-assisted molecular delivery, the construct comprising:

• a targeting domain and
• a sensor domain covalently bound to the targeting domain, the sensor domain comprising:
• a signal detection region complementary to at least one signal polynucleotide,
• a first chimeric sequence comprising at least one RNA region,
• a second chimeric sequence comprising a DNA region complementary to an RNA region of the at least one RNA regions of the first chimeric sequence, and
• a masking segment complementary to the first chimeric sequence;
• wherein the sensor domain is configured such that:
• in absence of the signal polynucleotide,
• the masking segment hybridizes with the first chimeric sequence,
• the DNA region of the second chimeric sequence is in a configuration not processable by RNase H, and
• the signal detection region is presented for binding to the signal polynucleotide;
• and
• in presence of the signal polynucleotide,
• the signal detecting region hybridizes with the signal polynucleotide,
• the masking segment is displaced from the first chimeric sequence, and
• the DNA region of the second chimeric sequence hybridizes with the complementary RNA region of the at least RNA region of the first chimeric sequence to provide an RNase H binding site presented for binding to RNase H, and
• the sensor domain is configured to allow release of the targeting domain from the sensor domain upon cleavage of the RNase H binding site by the RNase H.