Compositions and methods of using two-promoter vector for treatment of lysosomal storage disorders
OwnerHung DO, Lin LIU +1inventors
InventorsHung DO, Lin LIU, Andrew Charles HEDMAN
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Abstract
Provided are compositions comprising vectors for the co-expression of a modified GlcNAc-1-Phosphotransferase gene and a lysosomal enzyme. The gene encoding the lysosomal enzyme is operably linked to a first promoter and the gene encoding the GlcNAc-1-Phosphotransferase is operably linked to a second promoter. Also provided herein are methods of treating a lysosomal storage disorder comprising administering to a subject the compositions of the disclosure.
Claims21
(1-28.) canceled
A composition comprising a vector comprising a sequence encoding a first promoter operably linked to a first polynucleotide encoding a lysosomal enzyme and a second promoter operably linked to a second polynucleotide encoding a modified GlcNAc-1 phosphotransferase.
The composition of claim 1, wherein the vector is a viral vector.
The composition of claim 1, wherein the vector is a non-viral vector.
The composition of claim 1, wherein the vector is an adenoviral vector or an adeno-associated viral (AAV) vector.
The composition of claim 1, wherein the vector is a plasmid.
The composition of claim 1, wherein the first promoter is CBH and the second promoter is selected from EFS or JeT.
The composition of claim 1, wherein the first promoter is CMV and the second promoter is selected from PGK, JeT, or EF1-α.
The composition of claim 1, wherein the modified GlcNAc-1 phosphotransferase comprises S1S3 PTase.
The composition of claim 1, wherein the lysosomal enzyme is selected from the group consisting of b-glucocebrosidase (GBA), Galactosylceremidase (GALC), a-Galactosidase (GLA), a-N-acetylglucosaminidase (NAGLU), acid a-glucosidase (GAA), lysosomal acid a-mannosidase (LAMAN), and HexM.
A method of treating a lysosomal storage disorder (LSD), the method comprising administering to a subject an effective amount of a composition of claim 1, wherein the composition increases the phosphorylation of a lysosomal enzyme responsible of the LSD, thereby treating the LSD.
The method of claim 10, wherein the subject has been diagnosed with the LSD.
The method of claim 10, wherein the subject presents a sign or symptom of the LSD.
A method of preventing an occurrence or an onset of a lysosomal storage disorder (LSD), the method comprising administering to a subject an effective amount of a composition of claim 1, wherein the composition increases the phosphorylation of a lysosomal enzyme responsible of the LSD, thereby preventing the occurrence of the LSD in the subject.
The method of claim 13, wherein the subject is at risk of the occurrence or the onset of the LSD.
The method of claim 13, wherein the subject presents a sign or a symptom of the LSD.
A method of ameliorating the phosphorylation of a lysosomal enzyme responsible for a lysosomal storage disorder (LSD), the method comprising contacting to a cell, an effective amount of a composition of claim 1, wherein the composition increases the phosphorylation of the lysosomal enzyme.
The method of claim 16, wherein the cell is in vitro or ex vivo.
The method of claim 16, wherein a subject comprises the cell.
The method of claim 18, wherein the subject presents a sign or a symptom of the LSD.
The method of claim 18, wherein the subject is at risk of the occurrence or the onset of the LSD.
Dependencies are inferred from the claim text.