The present invention relates to the field of bio-production of hyaluronic acid.

There is a need in the art for hyaluronic acid production methods allowing its highly efficient synthesis and secretion.

The solution proposed in the present invention is the use of a genetically modified cell comprising many modifications as described in the present text.

The present invention further proposes methods allowing the bio-production of hyaluronic acid having a controlled molecular weight using the genetically modified cells of the invention.

The present invention relates to the use of glutamine synthetase as a protein therapy (such as enzyme replacement protein therapy) for the treatment of hyperammonemia. In particular the invention relates to the systemic administration of glutamine synthetase. The glutamine synthetase may be provided in conjugated or fusion form, to increase its half-life in the circulation. Also provided is a pharmaceutical composition comprising glutamine synthetase. The invention also relates to the uses, methods, and compositions involving a combination of the glutamine synthetase protein and an ammonia lowering agent, such as a nitrogen scavenger.

The present invention provides methods and compositions for stable genetic modification of cultured mammalian cells. The genetic modifications can be used to produce cultured mammalian cells for therapeutic or diagnostic purposes.

Genetically engineered bacteria which express RNAs or proteins that produce ammonia upon decreases in phosphate concentrations are disclosed.

A non-naturally occurring cell comprising an inoperative genomic asparaginase (Aspg) gene and an inoperative glutamine synthetase (Gs) gene, wherein the cell has been transfected with a controllably expressed gene encoding an enzyme having asparaginase activity, a controllably expressed gene encoding an enzyme having glutamine synthetase activity, and a controllably expressed gene encoding a heterologous protein of interest.

The present invention relates to the use of glutamine synthetase as a protein therapy (such as enzyme replacement protein therapy) for the treatment of hyperammonemia. In particular the invention relates to the systemic administration of glutamine synthetase. The glutamine synthetase may be provided in conjugated or fusion form, to increase its half-life in the circulation. Also provided is a pharmaceutical composition comprising glutamine synthetase. The invention also relates to the uses, methods and compositions involving a combination of the glutamine synthetase protein and an ammonia lowering agent, such as a nitrogen scavenger.

Methods, formulations, and applications of treating and preventing hyperammonemia by reducing ammonia levels are provided, which also have implications for reducing hemodialysis.

The invention relates to a modified mammalian glutamine synthetase comprising a mutation at amino acid position 10 and/or 298 in a mammalian glutamine synthetase, wherein the mutation is selected from the group consisting of R298K, N10S, N10T and N10Q and to an expression vector, a nucleic acid and a eukaryotic host cell encoding said modified mammalian glutamine synthetase and to its use as a selection marker. The invention further relates to methods for preparing stable cell lines, or for producing a protein of interest using said modified mammalian glutamine synthetase for selection.

Provided are a theanine-producing strain and use thereof in tea fermentation production. A corynebacterium glutamicum is proposed, which includes an alanine decarboxylase CsAlaDC mutant. The theanine-producing strain is obtained by taking the corynebacterium glutamicum as a starting strain, knocking out in sequence an -ketoglutarate dehydrogenase E1 subunit gene odhA, a glutamate external transporter gene Ncg11221 and a lactate dehydrogenase gene ldh; and/or expressesing a citrate synthase gene gltA, a pyruvate kinase gene pyk and a glutamate dehydrogenase gene gdh; and/or overexpressing an alanine dehydrogenase alaA and integrating a -glutamine synthetase GMAS into a cg1960 pseudogene locus of the corynebacterium glutamicum.

A polynucleotide with a selection marker sequence under the control of a desirable HSVMin promoter leads to improved efficiency for biotechnology applications. The polynucleotide may, for example, be a transposon for use with Tc1/mariner systems. Through various embodiments of the present disclosure, one is able to efficiently and effectively introduce cargo regions from polynucleotides such as those carrying a glutamine synthetase gene into a host's DNA.