Stick-based methods for aptamer-mediated siRNA targeted delivery

Despite the therapeutic utility of small interfering RNA (siRNA) molecules, the development of a safe and reliable method to selectively target diseased organs and tissues is still a critical need for their translation to the clinic. Here we describe how nucleic acid-based aptamers against cell surface epitopes may be used to address this issue. We discuss the most recent examples and advances in the field of aptamer siRNA delivery and provide a fast and simple protocol for the design and generation of aptamer-siRNA chimeras. The described approach is based on the annealing of the targeting aptamer, and the antisense strand through “stick” complementary sequences elongated at their 3′ end, and the subsequent paring with the sense strand. Such a protocol allows a modular non-covalent generation of the constructs and permits an efficient delivery of the siRNA moiety into aptamer target cells.