The present invention is related to a compound that includes (a) α-L-iduronidase (IDUA), fragment, or analog thereof and (b) a targeting moiety, for example, where compound is a fusion protein including IDUA and Angiopep-2. In certain embodiments, these compounds, owning to the presence of the targeting moiety can crossing the blood-brain barrier or accumulate in the lysosome more effectively than the enzyme alone. The invention also features methods for treating mucopolysaccharidosis type I (MPS-I) using such compounds.