Project Summary Nucleic acid aptamers (aptamers) have been used as therapeutic agents or delivery ligands for various biomedical applications such as regenerative medicine, cancer therapy, molecular biosensing, cell delivery, detoxification, anti-inflammation, anti-coagulation, etc. However, the success of these applications largely depends on the discovery and delivery of high-affinity and high-specificity aptamers, which remains challenging today. Therefore, the objective of this project is to study an innovative method for aptamer selection and truncation, and to further examine the efficiency of in vivo aptamer delivery in regulating inflammation. We will work on four specific aims to achieve the objective. In the first three aims, we will focus on aptamer selection and truncation. Notably, while these three aims are related to one another, the proposed research activities in these aims can be conducted independently. After the selection and truncation of high-quality aptamers, we will examine microneedle-mediated aptamer delivery for local, defined treatment of inflammation using an animal model. The success of this project will not only lead to the development of a technological platform for therapeutic aptamer discovery, but also pave a new way of fighting against inflammatory cytokines in the treatment of complicated immune disorders.