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New Platform Technology for the Development of Therapeutic Proteins and Antibodies Yong-Sung Kim Dept. of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea. Tel: +82-31-219-2662; Fax: +82-31-219-2394; E-mail: [email protected]. In this talk, I would like to introduce our efforts to establish new platform technology for the development of therapeutic proteins and antibodies, which have been established in our group for the last several years. Those are 1) Novel protein scaffold development as an alternative to antibody and 2) Interfering transbody, which can penetrate into living cells and selectively degrade targeted mRNA to resulting in gene-silencing effect. For the first topic, I will introduce a novel non-antibody protein scaffold based on human Kringle domain. Due to the limits of mAbs in terms of stability, solubility, manufacturing cost, intellectual property, etc., alternative non-antibody scaffolds have been developed to have ability to specifically bind to given targets, like antibody, but overcome the limits of antibody. We have developed Kringle domain variants to function as agonists against TRAIL receptors, death receptor 5 (DR5) and 4 (DR4) as well as antagonists against tumor necrosis factor-alpha. I will deliver the biochemical/biophysical properties of Kringle domain variants and the in vitro and in vivo biological efficacy. For the second topic, I will introduce a novel proof-of-concept technology, we termed as 'interfering transbody', in which a cell-penetrating antibody (transbody) specifically hydrolyzes targeted mRNAs in the cellular cytosol and leads to targeted gene silencing. Targeting particular mRNAs for degradation is a fascinating approach to achieve gene silencing. I will convince you that interfering transbody could have potential applications in anti-cancer or anti-viral therapies.