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, Heejin Kim, Yoonmi Lee, Su Yeon Lee, Insup Noh, Xiao Yan Li, Stephen J. Weiss, Tae Ahn Jahng, Jong In Yook

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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 invivo. 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.

Original languageEnglish
Pages (from-to)9888-9896
Number of pages9
JournalBiomaterials
Volume35
Issue number37
DOIs
Publication statusPublished - 2014 Dec 1

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Intercellular Signaling Peptides and Proteins
Proteins
Polypeptides
Bone Morphogenetic Protein 7
Furin
Tissue regeneration
Peptides
Bone Regeneration
Pharmacokinetics
Epithelial-Mesenchymal Transition
Prodrugs
Regeneration
Bone
Therapeutics
Processing

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Kim, N. H., Cha, Y. H., Kim, H. S., Lee, S. E., Huh, J. K., Kim, J. K., ... Yook, J. I. (2014). A platform technique for growth factor delivery with novel mode of action. Biomaterials, 35(37), 9888-9896. https://doi.org/10.1016/j.biomaterials.2014.08.005
Kim, Nam Hee ; Cha, Yong Hoon ; Kim, Hyun Sil ; Lee, Soo Eon ; Huh, Jong Ki ; Kim, Jung Kook ; Kim, Jeong Moon ; Ryu, Joo Kyung ; Kim, Heejin ; Lee, Yoonmi ; Lee, Su Yeon ; Noh, Insup ; Li, Xiao Yan ; Weiss, Stephen J. ; Jahng, Tae Ahn ; Yook, Jong In. / A platform technique for growth factor delivery with novel mode of action. In: Biomaterials. 2014 ; Vol. 35, No. 37. pp. 9888-9896.
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Kim, NH, Cha, YH, Kim, HS, Lee, SE, Huh, JK, Kim, JK, Kim, JM, Ryu, JK, Kim, H, Lee, Y, Lee, SY, Noh, I, Li, XY, Weiss, SJ, Jahng, TA & Yook, JI 2014, 'A platform technique for growth factor delivery with novel mode of action', Biomaterials, vol. 35, no. 37, pp. 9888-9896. https://doi.org/10.1016/j.biomaterials.2014.08.005

A platform technique for growth factor delivery with novel mode of action. / Kim, Nam Hee; Cha, Yong Hoon; Kim, Hyun Sil; Lee, Soo Eon; Huh, Jong Ki; Kim, Jung Kook; Kim, Jeong Moon; Ryu, Joo Kyung; Kim, Heejin; Lee, Yoonmi; Lee, Su Yeon; Noh, Insup; Li, Xiao Yan; Weiss, Stephen J.; Jahng, Tae Ahn; Yook, Jong In.

In: Biomaterials, Vol. 35, No. 37, 01.12.2014, p. 9888-9896.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A platform technique for growth factor delivery with novel mode of action

AU - Kim, Nam Hee

AU - Cha, Yong Hoon

AU - Kim, Hyun Sil

AU - Lee, Soo Eon

AU - Huh, Jong Ki

AU - Kim, Jung Kook

AU - Kim, Jeong Moon

AU - Ryu, Joo Kyung

AU - Kim, Heejin

AU - Lee, Yoonmi

AU - Lee, Su Yeon

AU - Noh, Insup

AU - Li, Xiao Yan

AU - Weiss, Stephen J.

AU - Jahng, Tae Ahn

AU - Yook, Jong In

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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 invivo. 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.

AB - 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 invivo. 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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