Lysosomal protein targeting sequence and therapeutic applications of same

摘要

The present disclosure relates to methods of treating diseases states such as lysosomal storage diseases and/or neurodegenerative diseases. Also disclosed are one or more compositions that may be useful for one or more of the disclosed methods, including compositions that may comprise acid β-glucosidase (GCase) protein comprising one or more mutations, peptides of acid β-glucosidase, and DNA vectors and cell lines related to acid β-glucosidase peptides or proteins.

主权项

1. A glucocerebrosidase (GCase) comprising at least 85% sequence identity to human GCase amino acid sequence as set forth in SEQ ID NO: 2 comprising one or more mutations at a position selected from 397, 399, 400, 401, 402, 403, 407, 408, 409, and combinations thereof, wherein said mutation decreases LIMP-2 binding, wherein the residues at positions 399-403 with reference to SEQ ID NO: 2 comprise a sequence selected from ASPII (SEQ ID NO: 7), DSAII (SEQ ID NO: 8), DSPAI (SEQ ID NO: 9), DSPIA (SEQ ID NO: 10), ASPIA (SEQ ID NO: 11), ASPAA (SEQ ID NO: 12), ESAII (SEQ ID NO: 21), ESPAI (SEQ ID NO: 22), ESPIA (SEQ ID NO: 23), and wherein said GCase protein at position 407-409 of SEQ ID NO: 2 comprises a sequence selected from AAA, AKA, TAD, and TAE.