Physicochemical and Biological Characterization of rhC1INH Expressed in CHO Cells

The disfunction or deficiency of the C1 esterase inhibitor (C1INH) is associated with hereditary or acquired angioedema (HAE/AAE), a rare life-threatening condition characterized by swelling in the skin, respiratory and gastrointestinal tracts. The current treatment options may carry the risks of ei...

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Autores principales: Ekaterina Zubareva, Maksim Degterev, Alexander Kazarov, Maria Zhiliaeva, Ksenia Ulyanova, Vladimir Simonov, Ivan Lyagoskin, Maksim Smolov, Madina Iskakova, Anna Azarova, Rahim Shukurov
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/b7adc867c7b4424d92943805cd97fb6c
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Sumario:The disfunction or deficiency of the C1 esterase inhibitor (C1INH) is associated with hereditary or acquired angioedema (HAE/AAE), a rare life-threatening condition characterized by swelling in the skin, respiratory and gastrointestinal tracts. The current treatment options may carry the risks of either viral infection (plasma-derived Berinert<sup>®</sup>) or immune reaction (human recombinant C1INH from rabbit milk, Ruconest<sup>®</sup>). This study describes the physicochemical and biological characterization of a novel recombinant human C1 esterase inhibitor (rhC1INH) from Chinese hamster ovary (CHO) cells for the treatment of hereditary angioedema compared to the marketed products Berinert<sup>®</sup> and Ruconest<sup>®</sup>. The mass spectrometry results of total deglycosylated rhC1INH revealed a protein with a molecular mass of 52,846 Da. Almost full sequence coverage (98.6%) by nanoLC-MS/MS peptide mapping was achieved. The purity and C1s inhibitory activity of rhC1INH from CHO cells are comparable with Ruconest<sup>®</sup>, although we found differences in charge isoforms distribution, intact mass values, and N-glycans profile. Comparison of the specific activity (IC<sub>50</sub> value) of the rhC1INH with human C1 esterase inhibitor from blood serum showed similar inhibitory properties. These data allow us to conclude that the novel rhC1INH molecule could become a potential therapeutic option for patients with HAE/AAE.