A platform technique for growth factor delivery with novel mode of action.
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.
['Kim|Nam Hee|NH|', 'Cha|Yong Hoon|YH|', 'Kim|Hyun Sil|HS|', 'Lee|Soo Eon|SE|', 'Huh|Jong-Ki|JK|', 'Kim|Jung Kook|JK|', 'Kim|Jeong Moon|JM|', 'Ryu|Joo Kyung|JK|', 'Kim|Hee-Jin|HJ|', 'Lee|Yoonmi|Y|', 'Lee|Su Yeon|SY|', 'Noh|Insup|I|', 'Li|Xiao-Yan|XY|', 'Weiss|Stephen J|SJ|', 'Jahng|Tae-Ahn|TA|', 'Yook|Jong In|JI|']
D000818:Animals D055396:Bone Morphogenetic Protein 2 D001861:Bone Regeneration D002460:Cell Line D004285:Dogs D005260:Female D045683:Furin D006801:Humans D051379:Mice D010455:Peptides D011993:Recombinant Fusion Proteins D011994:Recombinant Proteins D044968:Regenerative Medicine D014161:Transduction, Genetic D016212:Transforming Growth Factor beta D060449:Wnt Signaling Pathway
Growth factors Mode of action (MoA) Protein transduction domain (PTD) Regenerative medicine