Targeted therapeutic lysosomal enzyme fusion proteins and uses thereof

摘要

The present invention relates in general to therapeutic fusion proteins useful to treat lysosomal storage diseases and methods for treating such diseases. Exemplary therapeutic fusion proteins comprise a lysosomal enzyme, a lysosomal targeting moiety, e.g., an IGF-II peptide, and a spacer peptide. Also provided are compositions and methods for treating Mucopolysaccharidosis Type IIIB (Sanfilippo B Syndrome), comprising a targeted therapeutic fusion protein comprising alpha-N-acetylglucosaminidase (Naglu), a lysosomal targeting moiety, e.g., an IGF-II peptide, and a spacer peptide.

主权项

1. A targeted therapeutic fusion protein comprising (i) a human α-N-acetylglucosaminidase (Naglu) protein comprising amino acids 1-743 or 24-743 of SEQ ID NO:1, (ii) a peptide tag comprising SEQ ID NO: 2 or amino acids 8-67 of SEQ ID NO:5and (iii) a spacer peptide located between the Naglu protein and the peptide tag, wherein the spacer peptide comprises the amino acid sequence GAPGGGSPAPAPTPAPAPTPAPAGGGPSGAP (SEQ ID NO: 51).