Described herein are methods and compositions for treating a glucose 6 phosphatase deficiency based on mRNA therapy.

The invention relates to a process for the manufacturing and purification of recombinant enzyme products, in particular of food enzyme products and the use thereof. The invention particularly relates to a process for the processing of enzyme products from a microbial fermentation broth by methods of separation, enzymatic treatment and filtration procedures.

The present application provides materials and methods for treating a patient with Glycogen Storage Disease type la (GSD1a) both ex vivo and in vivo. In addition, the present application provides materials and methods for modulating the expression, function, and/or activity of the glucose-6-phosphatase, catalytic (G6PC) and/or the glucose-6-phosphatase (G6Pase) protein in a cell by genome editing.

Recombinant viruses, such as adeno-associated virus (rAAV) or lentivirus, for the treatment of glycogen storage disease type Ib (GSD-Ib) are described. The recombinant viruses use either the human glucose-6-phosphatase (G6PC) promoter/enhancer (GPE) or the minimal human G6PT promoter/enhancer (miGT) to drive expression of human glucose-6-phosphate transporter (G6PT). The disclosed vectors are capable of delivering the G6PT transgene to the liver and correcting metabolic abnormalities in a murine model of GSD-Ib. The recombinant virus-treated mice maintained glucose homeostasis, tolerated a long fast, and did not elicit anti-G6PT antibodies. Methods of treating a subject diagnosed with GSD-Ib using the recombinant viruses is further described.

Modified G6PC (glucose-6-phosphatase, catalytic subunit) nucleic acids and glucose-6-phosphatase- (G6Pase-) enzymes with increased phosphohydrolase activity are described. Also described are vectors, such as adeno-associated virus (AAV) vectors, and recombinant AAV expressing modified G6Pase-. The disclosed AAV vectors and rAAV can be used for gene therapy applications in the treatment of glycogen storage disease, particularly glycogen storage disease type Ia (GSD-Ia), and complications thereof.

The present invention provides a novel antisense oligonucleotide and a composition for preventing or treating glycogen storage disease type Ia. The present invention provides an antisense oligonucleotide which hybridizes with a pre-mRNA sequence derived from a region including at least one of a base at position 42911000, a base at position 42911004, and a base at position 42911005 in a base sequence of human chromosome 17 of GRCh38/hg38 and has activity to inhibit aberrant splicing of pre-mRNA of c.648G>T variant G6PC.

The present invention establishes a molecular therapy for glycogen storage disease type Ia. The present invention provides an oligonucleotide of 15-30 bases comprising a nucleotide sequence complementary to die cDNA of G6PC gene with c.648G>T mutation, wherein the oligonucleotide comprises a sequence complementary to a region comprising any site between the 82.sup.nd to the 92.sup.nd nucleotide from the 5 end of exon 5 of the G6PC gene with c.648C>T mutation, a pharmacologically acceptable salt or solvate thereof. Also provided is a pharmaceutical drug comprising the oligonucleotide, a pharmacologically acceptable salt or solvate thereof (e.g., therapeutic drug for glycogen storage disease type Ia).

Modified G6PC (glucose-6-phosphatase, catalytic subunit) nucleic acids and glucose-6-phosphatase- (G6Pase-) enzymes with increased phosphohydrolase activity are described. Also described are vectors, such as adeno-associated virus (AAV) vectors, and recombinant AAV expressing modified G6Pase-. The disclosed AAV vectors and rAAV can be used for gene therapy applications in the treatment of glycogen storage disease, particularly glycogen storage disease type Ia (GSD-Ia), and complications thereof.

The present disclosure provides antigen presenting polypeptide comprising a TGF-? MOD that is reversibly masked and acts as a TGF-? receptor agonist. The antigen presenting polypeptides comprising one or more chemical conjugation sites for incorporation of, for example, Type 1 Diabetes (T1D) associated epitope containing polypeptides. The antigen-presenting polypeptides and their T1D-associated epitope conjugates are useful for modulating the activity of a T-cell, and accordingly, the present disclosure provides methods of modulating activity of a T-cell in vitro and in vivo as a method of treatment of T1D.

The present application provides materials and methods for treating a patient with Glycogen Storage Disease type 1a (GSD1a) both ex vivo and in vivo. In addition, the present application provides materials and methods for modulating the expression, function, and/or activity of the glucose-6-phosphatase, catalytic (G6PC) and/or the glucose-6-phosphatase (G6Pase) protein in a cell by genome editing.