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From a manufacturing standpoint, although genetic fusion utilizes a simplified single-expression system, fusion constructs frequently require extensive, antigen-specific optimization because large or structurally complex antigens often express as insoluble aggregates or inclusion bodies, as exemplified by HBc fusions with SARS-CoV-2 RBD in which only low yields of soluble VLP were obtained without scaffold modification (Petrovskis et al., 2024)
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