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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 
Journal Title
Issue Date
Animals ; Bone Morphogenetic Protein 2/genetics* ; Bone Morphogenetic Protein 2/metabolism ; Bone Morphogenetic Protein 2/pharmacology ; Bone Regeneration/drug effects ; Cell Line ; Dogs ; Female ; Furin/metabolism ; Humans ; Mice ; Peptides/genetics* ; Peptides/metabolism ; Peptides/pharmacology ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/metabolism ; Recombinant Fusion Proteins/pharmacology ; Recombinant Proteins/genetics ; Recombinant Proteins/metabolism ; Recombinant Proteins/pharmacology ; Regenerative Medicine ; Transduction, Genetic/methods* ; Transforming Growth Factor beta/genetics* ; Transforming Growth Factor beta/metabolism ; Transforming Growth Factor beta/pharmacology ; Wnt Signaling Pathway/drug effects
Growth factors ; Mode of action (MoA) ; Protein transduction domain (PTD) ; Regenerative medicine
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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2. College of Dentistry (치과대학) > Research Institute (부설연구소) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral and Maxillofacial Surgery (구강악안면외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Kim, Hyun Sil(김현실) ORCID logo https://orcid.org/0000-0003-3614-1764
Kim, Hee Jin(김희진) ORCID logo https://orcid.org/0000-0002-1139-6261
Ryu, Ju Kyoung(유주경)
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Lee, Yoon Mi(이윤미)
Cha, Yong Hoon(차용훈) ORCID logo https://orcid.org/0000-0003-1761-3260
Huh, Jong Ki(허종기) ORCID logo https://orcid.org/0000-0002-7381-3972
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