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For protein or enzyme replacement therapy in monogenic disorders, the major risk factor for immunogenicity is the absence of residual (functional or non-functional) cross-reactive immunological material (CRIM), which could result in the complete lack of production of native protein, translating to a lack of tolerance to replacement therapy
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PLoS One 2018, 13 (8), e0201681 10.1371/journal.pone.0201681
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