Key result
Systemic rAAVrh74.CMV.GNE stimulates muscle GNE expression to endogenous levels, outperforming muscle-specific promoters.
Why the study?
Assays were needed to demonstrate the potency of AAV gene therapy vectors in producing sialic acid and to define the dose required for human GNE gene replacement in skeletal muscles.
Does AAV-mediated GNE gene replacement improve sialic acid biosynthesis and gene expression in GNE-deficient cell lines and wild-type mice?
Does AAV-mediated GNE gene replacement improve sialic acid biosynthesis and gene expression in GNE-deficient cell lines and wild-type mice?
AAV vectors with constitutive promoters like CMV can effectively deliver GNE gene replacement to skeletal muscles, providing a potential therapeutic strategy for GNE myopathy.
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Supports exploration of CMV-driven AAV for GNE myopathy gene therapy; leaves open clinical translation from mouse models.
Zygmunt et al. (2023) studied GNE myopathy (GNEM). AAV gene therapy vectors (rAAVrh74.CMV.GNE) vs. AAVs with muscle-specific promoters (MCK, MHCK7) was evaluated on Potency of AAV vectors to increase binding of Sia-specific lectins and GNE gene expression. Systemic delivery of rAAVrh74.CMV.GNE stimulated human GNE expression in muscles at levels equivalent to endogenous mouse Gne at a dose of 1x10^13 vg/kg, outperforming muscle-specific promoters.
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