The present disclosure describes improved adeno-associated virus (AAV) vectors for gene therapy applications in the treatment of glycogen storage disease, particularly glycogen storage disease type Ia (GSD-Ia). Described are recombinant nucleic acid molecules, vectors and recombinant AAV that include a G6PC promoter/enhancer, a synthetic intron, a G6PC coding sequence (such as a wild-type or codon-optimized G6PC coding sequence), and stuffer nucleic acid sequence situated between the G6PC promoter/enhancer and the intron, as well as between the intron and the G6PC coding sequence. The recombinant AAVs disclosed herein exhibit highly efficient liver transduction and are capable of correcting metabolic abnormalities in an animal model of GSD-Ia.

A method for preparing glucosamine includes the steps of converting fructose-6-phosphate (F6P) and an ammonium salt to glucosamine-6-phosphate (GlcN6P) under the catalysis of glucosamine-6-phosphate deaminase (EC 3.5.99.6, GlmD); and producing glucosamine (GlcN) by the dephosphorylation of GlcN6P under the catalysis of an enzyme capable of catalyzing the dephosphorylation. Such a method can be used to prepare glucosamine by in vitro enzymatic biosystem.

Described are methods for generating a reporter molecule in response to a target analyte in a cell-free system. A synthetic biological circuit is used to modify the level of the reporter molecule in response to the presence of the target analyte. The reporter molecule may be glucose or another molecule readily detected using a device such as glucose monitor or other portable sensor. Also provided are kits comprising a cell-free system with a synthetic biological circuit that generates or consumes a reporter molecule in response to a target analyte.

The present disclosure describes improved adeno-associated virus (AAV) vectors for gene therapy applications in the treatment of glycogen storage disease, particularly glycogen storage disease type Ia (GSD-Ia). Described are recombinant nucleic acid molecules, vectors and recombinant AAV that include a G6PC promoter/enhancer, a synthetic intron, a G6PC coding sequence (such as a wild-type or codon-optimized G6PC coding sequence), and stuffer nucleic acid sequence situated between the G6PC promoter/enhancer and the intron, as well as between the intron and the G6PC coding sequence. The recombinant AAVs disclosed herein exhibit highly efficient liver transduction and are capable of correcting metabolic abnormalities in an animal model of GSD-Ia.

The present disclosure describes improved adeno-associated virus (AAV) vectors for gene therapy applications in the treatment of glycogen storage disease, particularly glycogen storage disease type Ia (GSD-Ia). Described are recombinant nucleic acid molecules, vectors and recombinant AAV that include a G6PC promoter/enhancer, a synthetic intron, a G6PC coding sequence (such as a wild-type or codon-optimized G6PC coding sequence), and stuffer nucleic acid sequence situated between the G6PC promoter/enhancer and the intron, as well as between the intron and the G6PC coding sequence. The recombinant AAVs disclosed herein exhibit highly efficient liver transduction and are capable of correcting metabolic abnormalities in an animal model of GSD-Ia.

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.

A method for producing glucose and derivatives thereof by means of biotransformation with a recombinant yeast, which belongs to the technical field of synthetic biology. A construction method comprises any one of the following steps: i, knocking out metabolic pathway-related enzymes of glucose and derivatives thereof in a yeast strain; ii, enhancing or using an activity of synthetic pathway-related enzymes of glucose and derivatives thereof in the yeast strain; and iii, enhancing or using a capability of glucose and derivatives thereof in the yeast strain to enter and exit the yeast. Further provided are a recombinant yeast strain capable of producing glucose or derivatives thereof at a high yield and the use thereof in the conversion of a non-grain low-carbon carbon source. The low-carbon non-grain carbon source synthesized by means of using photoelectrocatalysis or traditional chemical industry is used as a substrate, and rapid preparation of food product raw materials glucose and derivatives thereof from the non-grain carbon source is realized by means of recombinant yeast cells.

This disclosure relates to mRNA therapy for the treatment of glycogen storage disease type 1a (GSD1a). mRNAs for use in the invention, when administered in vivo, encode glucose-6-phosphatase (G6PC). mRNA therapies of the disclosure increase and/or restore deficient levels of G6PC expression and/or activity in subjects.

This disclosure relates to mRNA therapy for the treatment of glycogen storage disease type 1a, (GSD-Ia), and related symptoms such as hypoglycemia. mRNAs for use in the invention, when administered in vivo, encode human glucose-6-phosphatase (G6Pase or G6PC), and functional fragments and variants thereof mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of G6PC expression and/or activity in subjects. mRNA therapies of the invention further increase the glucose production, and reduce the abnormal accumulation of glycogen and/or glucose-6-phosphate associated with GSD-Ia.

Disclosed herein are novel promoters that drive expression of a gene product preferentially in the heart and in skeletal muscle. Disclosed herein are vectors comprising these novel promoters and vectors comprising these novel promoters. Disclosed herein are methods of gene editing and gene therapy that employ these novel promoters and novel vectors.