Smart functional nucleic acid chimeras: Enabling tissue specific RNA targeting therapy

Lukas J Aaldering, Hossam Tayeb, Shilpa Krishnan, Susan Fletcher, Stephen D Wilton, Rakesh N Veedu

A major obstacle for effective utilization of therapeutic oligonucleotides such as siRNA, antisense, antimiRs etc. is to deliver them specifically to the target tissues. Toward this goal, nucleic acid aptamers are re-emerging as a prominent class of biomolecules capable of delivering target specific therapy and therapeutic monitoring by various molecular imaging modalities. This class of short oligonucleotide ligands with high affinity and specificity are selected from a large nucleic acid pool against a molecular target of choice. Poor cellular uptake of therapeutic oligonucleotides impedes gene-targeting efficacy in vitro and in vivo. In contrast, aptamer-oligonucleotide chimeras have shown the capacity to deliver siRNA, antimiRs, small molecule drugs etc. toward various targets and showed very promising results in various studies on different diseases models. However, to further improve the bio-stability of such chimeric conjugates, it is important to introduce chemically-modified nucleic acid analogs. In this review, we highlight the applications of nucleic acid aptamers for target specific delivery of therapeutic oligonucleotides.