Kotaro Yoshioka, MD, PhD
Department of Neurology and Neurological Science, Tokyo Medical and Dental University
Kotaro Yoshioka received his PhD in 2016 from Tokyo Medical and Dental University (Japan), where he has developed a unique double-stranded ASO technology, “Heteroduplex oligonucleotide (HDO)” in the laboratory of Takanori Yokota. His work revealed that new type of HDO for antimiR can silence the target microRNA in vivo more efficiently than the original single-stranded antimiR with a novel intracellular mechanism. To further pursue a potent therapeutic oligonucleotides targeting extrahepatic tissues, especially CNS, he has developed a novel neuroactive double-stranded ASO, overhanging duplex oligonucleotide (ODO), that enables highly efficient delivery not only to multiple tissues such as skeletal muscles, peripheral lymphocytes and intestines via systemic injections, but also to brain via intraventricular injection. In addition, his postdoctoral work revealed an additional carrier protein of ODO, transferrin and a unique cellular uptake pathway associated with transferrin-receptor. Moreover, this double-stranded HDO-technology via CSF route enables significant improvements of CNS-toxicities of ASO and increases therapeutic index in mice and cynomolgus monkeys. These crucial discoveries by Dr. Yoshioka allow for the regulating new type of target gene and tissues more efficiently and safely, especially in CNS by the new double-stranded oligonucleotides technology.