Using aptamers for targeted delivery of RNA therapies.

Abstract

RNA-based treatments that can silence, introduce, or restore gene expression to target human diseases are emerging as a new class of therapeutics. Despite their potential for use in broad applications, their clinical translation has been hampered by a need for delivery to specific cells and tissues. Cell targeting based on the use of aptamers provides an approach for improving their delivery to the desired sites of action. Aptamers are nucleic acid oligonucleotides with structural conformations that provide a robust capacity for the recognition of cell surface molecules and that can be used for directed targeting. Aptamers can be directly conjugated to therapeutic RNA molecules, in the form of aptamer-oligonucleotide chimeras, or incorporated into nanoparticles used as vehicles for the delivery of these therapeutics. Herein, we discuss the use of aptamers for cell-directed RNA therapies, provide an overview of different types of aptamer-targeting RNA therapeutics, and review examples of their therapeutic applications. Challenges associated with manufacturing and scaling up production, and key considerations for their clinical implementation, are also outlined.