Phosphodiester alpha-GlcNAcase of the lysosomal targeting pathway

A method of producing a phosphodiester α-GlcNAcase in a cell comprising

• transfecting into said cell a DNA construct comprising a targeting sequence homologous to a target site within or upstream of a endogenous phosphodiester α-GlcNAcase gene contained in the cell, wherein said endogenous gene comprises the sequence in SEQ ID NO:7, an exogenous regulatory sequence, an exon, and an unpaired splice-donor site at the 3′ end of the exon, wherein said transfecting generates a homologously recombinant cell in which the splice-donor site is operatively linked to the second exon of the endogenous gene, and the exogenous regulatory sequence controls transcription of the construct driven, the endogenous gene, and any sequence lying between the construct-driven exon and the endogenous gene, to produce a RNA transcript that encodes the phosphodiester α-GlcNAcase, so that the homologously recombinant cell produces the phosphodiester α-GlcNAcase.