Design and Biological Application of RTK Agonist Aptamers

Growth factors (GFs) play important roles in cell–cell communication by transducing cell signaling through binding to receptor tyrosine kinases (RTKs), single-pass transmembrane receptors with kinase activity. GF stimulates various cellular activities, such as proliferation, migration, and differentiation, to secure the developmental process and maintain tissue homeostasis. Owing to the regenerative action, recombinant GFs have been widely used in the treatment of disease and injured tissue. In addition, GF is supplemented in culture media to control cellular activity in vitro. However, recombinant GFs often suffer from their limitations such as high production cost, risk of contamination, and batch-to-batch activity variations. Aptamers are single-stranded oligonucleotides with molecular recognition ability that have attracted attention as a promising alternative. They can bind to target molecules with high affinity and specificity, which are often comparable to those of antibodies. RTK-binding aptamer can be generated through a well-established molecular evolution process called "systematic evolution of ligands by exponential enrichment" (SELEX) using a purified extracellular domain of receptor or receptor expressing cells. This chapter summarizes the RTK-binding aptamers and their applications in the modulation of RTK activity, particularly focusing on the generation and rational design of agonist aptamer to RTKs.