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A chemically unmodified agonistic DNA with growth factor functionality for in vivo therapeutic application, Project Assistant Professor Satoshi Uchida, Associate Professor Horacio Cabral, Department of Bioengineering, Momoko Akiyama(D2), Assistant Professor Ryosuke Ueki, Professor Shinsuke Sando, Department of Chemistry and Biotechnology, and other researchers.

Although growth factors have great therapeutic potential because of their regenerative functions, they often have intrinsic drawbacks, such as low thermal stability and high production cost. Oligonucleotides have recently emerged as promising chemical entities for designing synthetic alternatives to growth factors. However, their applications in vivo have been recognized as a challenge because of their susceptibility to nucleases and limited distribution to a target tissue. Here, we present the first example of oligonucleotide-based growth factor mimetics that exerts therapeutic effects at a target tissue after systemic injection. The aptamer was designed to dimerize a growth factor receptor for its activation and mitigated the progression of Fas-induced fulminant hepatitis in a mouse model. This unprecedented functionality of the aptamer can be reasonably explained by its high nuclease stability and migration to the liver parenchyma. These mechanistic analyses provided insights for the successful application of aptamer-based receptor agonists.

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