Objective:　Pompe　disease　is　a　lysosomal　glycogen　storage　disease　caused　by　acid　a-glucosidase　(GAA)　deficiency,　which　is　characterized　by　glycogen　accumulation　in　the　heart,　skeletal　muscle,　and　central　nervous　system　(CNS).　AAV　vector-mediated　gene　therapy　is　expected　to　be　a　breakthrough　in　the　treatment　of　Pompe　disease.　In　this　study,　AAV9　vector　was　used　to　mediate　GAA　gene　transfer　in　Pompe　disease　model　mice,　and　the　changes　of　GAA　protease　activity,　glycogen　accumulation　in　tissues　and　pathological　changes　in　mice　after　transgenic　intervention　were　evaluated.　Methods:　Codon　optimized　GAA　gene　(coGAA)　was　carried　by　AAV9　vector,　and　the　AAV　vector　was　packaged　by　baculovirus　production　process.　Adult　Pompe　model　mice　were　given　a　single　intravenous　injection　at　the　dose　of　1.　1　x　10-3,　3.0　x　10-3,　1.2　x　10-4　vg/kg,　and　aged　Pompe　model　mice　were　given　a　single　intravenous　injection　at　the　dose　of　3.　0　x　10-3　vg/kg.　After　reaching　the　end　point　of　the　experiment,　the　mice　were　euthanized,　GAA　protease　activity　was　determined　by　fluorescence　spectrophotometry,　glycogen　accumulation　was　observed　by　PAS　staining,　and　pathological　changes　were　detected　by　HE　staining.　Results:　Five　weeks　after　administration,　GAA　protein　was　widely　expressed　in　al　tissues　of　adult　model　mice,　with　higher　expression　levels　in　heart　and　liver,　and　lower　expression　levels　in　brain　and　spinal　cord.　After　rAAV9-coGAA　treatment,　glycogen　content　in　myocardium,　skeletal　muscle　and　brain　decreased,　ad　vacuolar　degeneration　in　myocardium　ad　skeletal　muscle　decreased　significantly.　After　treatment,　the　tissue　enzyme　activity　of　the　aged　animals　was　significantly　increased　compared　with　that　of　the　model　mice.　The　vacuolar　degeneration　and　inflammatory　cell　infiltration　of　the　myocardium　were　decreased,　but　the　pathological　improvement　of　skeletal　muscle　was　limited.　Conclusion:　A　single　intravenous　injection　of　rAAV9-coGAA　can　enhance　GAA　enzyme　activity,　reduce　glycogen　accumulation　and　improve　pathology　in　Pompe　model　mice.　The　therapeutic　effect　was　dose-dependent,　and　the　injection　also　had　certain　therapeutic　effect　on　aged　animals.　This　study　laid　a　theoretical　foundation　for　the　clinical　application　of　AAV9　mediated　gene　therapy　via　intravenous　route　in　Pompe　disease.　©　2022,　China　Biotechnology　Press.　All　rights　reserved.