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A platform technique for growth factor delivery with novel mode of action

 Nam Hee Kim  ;  Yong Hoon Cha  ;  Hyun Sil Kim  ;  Soo Eon Lee  ;  Jong-Ki Huh  ;  Jung Kook Kim  ;  Jeong Moon Kim  ;  Joo Kyung Ryu  ;  Hee-Jin Kim  ;  Yoonmi Lee  ;  Su Yeon Lee  ;  Insup Noh  ;  Xiao-Yan Li  ;  Stephen J. Weiss  ;  Tae-Ahn Jahng  ;  Jong In Yook 
 Biomaterials, Vol.35(37) : 9888-9896, 2014 
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Though growth factors allow tissue regeneration, the trade-off between their effectiveness and adverse effects limits clinical application. The key issues in current growth factor therapy largely derive from initial burst pharmacokinetics, rapid clearance, and proteolytic cleavage resulting in clinical ineffectiveness and diverse complications. While a number of studies have focused on the development of carriers, issues arising from soluble growth factor remain. In this study, we report a prodrug of growth factors constituting a novel mode of action (MoA). To mimic endogenous protein processing in cells, we developed a recombinant BMP-2 polypeptide based on a protein transduction domain (PTD) to transduce the protein into cells followed by furin-mediated protein cleavage and secretion of active growth factor. As proof of concept, a few micrograms scale of PTD-BMP-2 polypeptide sufficed to induce bone regeneration in vivo. As a simple platform, our technique can easily be extended to delivery of BMP-7 and DKK-1 as therapeutics for TGF-β and canonical Wnt signaling, respectively, to suppress the epithelial–mesenchymal transition (EMT), which constitutes a fundamental biological mechanism of many diseases. This technique largely overcomes the limitations of current soluble growth factors and opens the door to next generation growth factor therapeutics.
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5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral and Maxillofacial Surgery (구강악안면외과학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
김남희(Kim, Nam Hee) ORCID logo https://orcid.org/0000-0002-3087-5276
김현실(Kim, Hyun Sil) ORCID logo https://orcid.org/0000-0003-3614-1764
김희진(Kim, Hee Jin) ORCID logo https://orcid.org/0000-0002-1139-6261
유주경(Ryu, Ju Kyoung)
육종인(Yook, Jong In) ORCID logo https://orcid.org/0000-0002-7318-6112
이윤미(Lee, Yoon Mi)
차용훈(Cha, Yong Hoon) ORCID logo https://orcid.org/0000-0003-1761-3260
허종기(Huh, Jong Ki) ORCID logo https://orcid.org/0000-0002-7381-3972
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