Projects : RCMG Inc. | The Development of novel glycobiomarker/IVD

Glycomedicine

Glycans or glycosylations are known to be modification of biomolecules, including lipids, proteins, and low- or high-molecular chemicals. Glycosylations are regulated by glycosyltransferases and their substrates and acceptors, which are affected by cellular conditions, such as differentiation, development, ageing, diseases and individual genetic background. Thus, glycans have been considered as good indicators, “glycobiomarkers”.

In the Glycoscience, new technologies based on engineering in addition to biochemistry and molecular biology promote new findings in medicine. For instances, changes of glycan structures of proteins are common features of cancer cells, associated with carcinogenesis, invasion and metastasis. “Glycomics and Glycoproteomics”, the research of glycans and glycproteins, are emerging fields in the postgenome and postproteomics era.

Dr. Narimatsu was a director of Research Center of Medical Glycoscience at AIST, Japan, and a pioneer of establishing various technologies for glycoscience research. Technologies include, for instances, profiling the expression pattern of glycogenes, profiling glycan structures of glycoproteins, and identifying the glycan structure connected to a target glycoprotein. By using these technologies, the center successfully developed various glycobiomarkers. RCMG Inc. takes over the know-how and applies the strategies to develop novel biomarkers and IVDs. Our current research targets are inflammation, infectious diseases, and cancers, in which alterations of glycans would be detected.

References:

Angata K, Sawaki H, Tsujikawa S, Ocho M, Togayachi A, Narimatsu H.
Glycogene expression profiling of hepatic cells by RNA-Seq analysis for glyco-biomarker identification.
Front Oncol. 2020 Jul 28;10:1224. doi: 10.3389/fonc.2020.01224.

Narimatsu H.
Development of M2BPGi: a novel fibrosis serum glycobiomarker for chronic hepatitis/cirrhosis diagnostics.
Expert Rev Proteomics. 2015;12(6):683-93. doi: 10.1586/14789450.2015.1084874.

Ito H, Kuno A, Sawaki H, Sogabe M, Ozaki H, Tanaka Y, Mizokami M, Shoda J, Angata T, Sato T, Hirabayashi J, Ikehara Y, Narimatsu H.
Strategy for glycoproteomics: identification of glyco-alteration using multiple glycan profiling tools.
J Proteome Res. 2009 Mar;8(3):1358-67. doi: 10.1021/pr800735j.

Narimatsu H, Kaji H, Vakhrushev SY, Clausen H, Zhang H, Noro E, Togayachi A, Nagai- Okatani C, Kuno A, Zou X, Cheng L, Tao SC, Sun Y.
Current technologies for complex glycoproteomics and their applications to biology/disease- driven glycoproteomics.
J Proteome Res. 2018 Dec 7;17(12):4097-4112. doi: 10.1021/acs.jproteome.8b00515.

Narimatsu H, Sawaki H, Kuno A, Kaji H, Ito H, Ikehara Y.
A strategy for discovery of cancer glycobiomarkers in serum using newly developed technologies for glycoproteomics.
FEBS J. 2010 Jan;277(1):95-105. doi: 10.1111/j.1742-4658.2009.07430.x.

Hepatitis B Virus

Hepatitis B virus (HBV), one of the most human infected viruses, has been a global health problem¹. The HBV envelope protein is composed of three type of surface antigens, S-, M-, and L-HBsAg, which are produced from an HBsAg gene containing PreS1, PreS2, and S-domains². HBsAgs are modulated by the chain of saccharides, such as N-glycan and O-glycan, which are involved in secretion and stability of the virus^3,4. Recent glycotechnology revealed the difference of glycosylation in each HBsAg. PreS2 domain is present in M-HBsAg and L- HBsAg, the former contains O-glycan in PreS2 but the latter does not, in genotype C^5,6. A recombinant monoclonal antibody against HBsAg glycan isomer (HBsAgGi) was cloned and available from RCMG Inc.
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Technologies used in HBsAgGi development

Glycome analysis to identify the structure of glycans
Synthesis of glycosylated peptide
Generating glycosylated HBsAg proteins
Generating recombinant monoclonal antibody

Our targets in HBV
Infectious HBV particles (Dane particles) containing HBV DNA are less abundant than
subviral particles (SVP) in HBV patients, i.e. Dane particle <<< SVP. To monitor the presence of infectious HBV, technology measuring only Dane particle would be necessary rather than measuring whole HBV particles containing non-infectious SVP. Currently, nucleos(t)ide analogs (NA) treatment has been approved for the patients with chronic hepatitis B. NA treatment reduces HBV DNA, resulting in HBV RNA containing HBV particles, which might be infectious⁷,. Thus, convenient measuring method for HBV containing HBV RNA will be useful. Since HBsAgGi recognizes PreS2 domain in M-HBsAg of genotype C, following are current targets using HBsAgGi.

References:

1. https://www.who.int/news-room/fact-sheets/detail/hepatitis-b
2. Schadler and Hildt (2009) Viruses 1:185-209. doi: 10.3390/v1020185.
3. Schmitt et al. (2004) J Gen Virol 85:2045-2053. doi: 10.1099/vir.0.79932-0.
4. Dobrica et al. (2020) Cells 9:1404. doi: 10.3390/cells9061404.
5. Wagatsuma et al. (2018) Anal Chem 90:10196-10203. doi: 10.1021/acs.analchem.8b01030
6. Angata et al. (2021) Biochim Biophys Acta Gen Subj. In Press. doi:10.1016/j.bbagen.2021.130020
7. Wang et al. (2016) J Hepatol. 65:700-710. doi: 10.1016/j.jhep.2016.05.029.

RCMG Inc.

2-1-6 Sengen, Plaza suite 209, Tsukuba, Ibaraki 305-0047
TEL：+81-29-828-8010

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Glycomedicine

References:

Hepatitis B Virus

IVD by using HBsAgGi