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Development of a New Type of Recombinant Hyaluronidase Using a Hexahistidine; Possibilities and Challenges in Commercialization

  • Park, Chaeri (College of Pharmacy, Catholic University of Daegu) ;
  • Song, Yun-Kyoung (College of Pharmacy, Catholic University of Daegu) ;
  • Kim, Young-Hyun (National Primate Research Center & Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Jung, Yena (College of Pharmacy, Catholic University of Daegu) ;
  • Park, Young-Ho (National Primate Research Center & Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Song, Bong-Seok (National Primate Research Center & Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Eom, Taekil (College of Applied Life Sciences, the Research Institute for Subtropical Agriculture and Biotechnology, Jeju National University) ;
  • Kim, Ju-Sung (College of Applied Life Sciences, the Research Institute for Subtropical Agriculture and Biotechnology, Jeju National University) ;
  • Kim, Sang-Hyun (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Kim, Ji-Su (National Primate Research Center & Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Sun-Uk (National Primate Research Center & Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Sang-Rae (National Primate Research Center & Futuristic Animal Resource and Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Ekyune (College of Pharmacy, Catholic University of Daegu)
  • Received : 2019.05.22
  • Accepted : 2019.07.25
  • Published : 2019.08.28

Abstract

Hyaluronidases enhance therapeutic drug transport by breaking down the hyaluronan barrier to lymphatic and capillary vessels, facilitating their tissue absorption. Commercially available hyaluronidases are bovine in origin; however, they pose risks such as bovine spongiform encephalopathy. The present study aimed to develop a novel, highly active hyaluronidase and assess its function. Therefore, in order to find the most efficient active hyaluronidase, we produced several shortened hyaluronidases with partial removal of the N- or C-terminal regions. Moreover, we created an enzyme that connected six histidines onto the end of the hyaluronidase C-terminus. This simplified subsequent purification using $Ni^{2+}$ affinity chromatography, making it feasible to industrialize this highly active recombinant hyaluronidase which exhibited catalytic activity equal to that of the commercial enzyme. Therefore, this simple and effective isolation method could increase the availability of recombinant hyaluronidase for research and clinical purposes.

Keywords

References

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