~Development of a homodivalent VHH FGFR1 agonist molecule with higher thermal and structural stability than natural FGF2, unveiled at JBC - Aiming for VHH-based supplement applications in the field of regenerative medicine - ~
Epsilon Molecular Engineering Co., Ltd. (Headquarters: Saitama City, Saitama Prefecture, President and CEO: Naoto Nemoto, hereinafter referred to as "the Company") is pleased to announce that a scientific paper on a substitute for the bioactive protein human Fibroblast Growth Factor-2 (hereinafter referred to as "FGF2" (*2)), composed of camelid-derived VHH (*1), which was jointly developed with Sekisui Chemical Co., Ltd. (Headquarters: Osaka City, Osaka Prefecture, President and CEO: Keita Kato), was published online in the Journal of Biological Chemistry on December 16, 2022 (local time) (https://www.jbc.org/article/S0021-9258(22)01247-9/fulltext#secsectitle0160). The Journal of Biological Chemistry is an internationally peer-reviewed open-access journal in the fields of biochemistry and molecular biology.
VHH is a single-domain antibody that utilizes the variable region of heavy chain antibodies produced by camelid animals. Due to its excellent physical properties (antigen-binding specificity, affinity, thermal stability, etc.), it is expected to be a next-generation antibody. Our company and Sekisui Chemical have jointly developed VHH as a substitute for FGF2. By deploying our proprietary core technology, cDNA display technology (*3), we efficiently obtained VHH that specifically binds to FGF receptor 1 (hereinafter referred to as "FGFR1"), and then created homobivalent VHH through protein engineering optimization. Sekisui Chemical also conducted biological activity evaluations of homobivalent VHH, including cell proliferation tests on fibroblasts. As a result, homobivalent VHH had a specific activity comparable to that of natural FGF2 and functioned as an FGF2 substitute. This FGF2 substitute is a novel FGFR1 agonist VHH.
Currently, FGF2 is commonly used in in vitro cell proliferation processes for regenerative medicine applications. However, due to its low thermal stability, the large amount of natural FGF2 recombinant protein required in the entire process poses a cost problem. The FGF2 substitute developed in this study has been found to have thermal stability more than 10°C higher than natural FGF2 recombinant protein. Furthermore, it is produced efficiently by microorganisms such as E. coli and yeast, making it possible to reduce the cost of cell culture medium additives in regenerative medicine research.
Paper title:
A novel agonist with homobivalent single domain antibodies that bind the FGF receptor-1 domain III functions as a FGF2 ligand
Author:
Ryo Yonehara, Shigefumi Kumachi, Kenji Kashiwagi, Kanako Wakabayashi-Nakao, Maiko Motohashi, Taihei Murakami, Teruhiko Yanagisawa, Hidenao Arai, Akikazu Murakami, Yukio Ueno, Naoto Nemoto, Masayuki Tsuchiya
Journal of Biological Chemistry, (2023) Volume 299, Issue 2, 102804
DOI: https://doi.org/10.1016/j.jbc.2022.102804
(*1) VHH: The variable region of an antibody (heavy chain antibody) composed solely of heavy chains found in camelid animals (llamas and alpacas) is called the Variable domain of heavy chain of heavy chain antibody or single-domain antibody. It has superior stability and modifiability compared to ordinary antibodies.
(*2) FGF2: Fibroblast Growth Factor 2. Also known as basic fibroblast growth factor; bFGF. A growth factor that exhibits multifaceted effects, such as regulating the ON/OFF state of intracellular signals by binding to FGF receptors. In the field of regenerative medicine, it is an important component of human embryonic stem cell culture medium, and FGF2 is necessary to maintain cells in an undifferentiated state.
(*3) cDNA display technology: A technology that allows the acquisition of target proteins in vitro by matching genotypes/phenotypes. It is possible to screen 10¹³-¹⁴ (10 trillion to 100 trillion) types of molecules at once.
The news release is available here.
About Epsilon Molecular Engineering Co., Ltd.
Epsilon Molecular Engineering Co., Ltd. (EME) is a Saitama University-certified venture company that has been developing innovative modality pharmaceuticals based on evolutionary molecular engineering since 2016. Leveraging its unique screening technology and molecular design methods, EME engages in collaborative research and development not only in pharmaceutical development but also in diagnostic agents and regenerative medicine reagents. With the corporate mission of "Creating the future with biomolecules," EME aims to contribute broadly to society and people's lives.
Homepage: https://www.epsilon-mol.co.jp/
*The EME logo is a registered trademark of Epsilon Molecular Engineering Co., Ltd.
[Contact from the press]
Epsilon Molecular Engineering Co., Ltd., Pharmaceutical Development Division, Business Development Section
E-mail: biz_dev@epsilon-mol.co.jp
[Contact information for inquiries regarding this product/service]
Epsilon Molecular Engineering Co., Ltd., Pharmaceutical Development Division, Business Development Section
E-mail: biz_dev@epsilon-mol.co.jp