8 research outputs found

    Functional biohybrid amphiphiles

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    Contains fulltext : 35856.pdf (publisher's version ) (Open Access

    Do enzymes sleep and work?

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    Contains fulltext : 35945.pdf (publisher's version ) (Open Access

    Synthesis and single enzyme activity of a clicked lipase-BSA hetero-dimer

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    Contains fulltext : 35329.pdf (publisher's version ) (Open Access

    In vitro and in vivo immunogenicity assessment of protein aggregate characteristics

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    The immunogenicity risk of therapeutic protein aggregates has been extensively investigated over the past decades. While it is established that not all aggregates are equally immunogenic, the specific aggregate characteristics, which are most likely to induce an immune response, remain ambiguous. The aim of this study was to perform comprehensive in vitro and in vivo immunogenicity assessment of human insulin aggregates varying in size, structure and chemical modifications, while keeping other morphological characteristics constant. We found that flexible aggregates with highly altered secondary structure were most immunogenic in all setups, while compact aggregates with native-like structure were found to be immunogenic primarily in vivo. Moreover, sub-visible (1-100 µm) aggregates were found to be more immunogenic than sub-micron (0.1-1 µm) aggregates, while chemical modifications (deamidation, ethylation and covalent dimers) were not found to have any measurable impact on immunogenicity. The findings highlight the importance of utilizing aggregates varying in few characteristics for assessment of immunogenicity risk of specific morphological features and may provide a workflow for reliable particle analysis in biotherapeutics.Drug Delivery Technolog
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