The present invention relates to topical glycosaminoglycan compositions, particularly hyaluronan compositions, that facilitate the penetration of modified glycosaminoglycans through the skin barrier into the epidermal and dermal layers of the skin, thereby allowing for the dermal administration of a glycosaminoglycan, such as hyaluronan, without requiring an injection. Through their ability to deliver hyaluronan to the epidermal and dermal layers, the present formulations are therefore suitable for use in dermal rejuvenation, enhancement, hyaluronan replenishment and protection therapy. The glycosaminoglycan compositions are also useful as delivery devices to facilitate the dermal and transdermal delivery of cosmetically and pharmaceutically active substances, including pharmaceuticals, polypeptides, proteins and similarly sized biomacromolecules, through the skin barrier.

The present invention relates to a method for the production of hyaluronic acid (HA) in Bacillus subtilis and Escherichia coli through plasmid vectors wherein the gene is under the control of strong promoter Pgrac, and a system for the selection of stable bacterial strains for the production of high levels of hyaluronic acid.

The present disclosure relates to recombinant viral vectors, to pharmaceutical compositions comprising such recombinant vectors, and to methods for prevention and treatment of osteoarthritis in mammals. In particular, this disclosure provides adeno-associated virus (AAV) vectors capable of expressing, in a host, osteoprotective/chondroprotective bioactive proteins, including hyaluronan synthase 2 (HAS2) and lubricin (PRG4). Methods of production of these AAV are provided, as are methods of treatment of osteoarthritis in mammalian joints, by the long-term gene expression of osteoprotective/chondroprotective proteins, including HAS2 and PRG4, in both synovial and chondrocyte cells.

A method of producing hyaluronic acid (HA) in Escherichia coli and Bacillus megaterium through episomal plasmid vectors wherein the gene is under the control of strong promoter T7, preferably under the control of strong promoter T7 of bacteriophage T7, and a system for the selection of stable bacterial strains producing high levels of hyaluronic acid, are provided.

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 Corynebacterium glutamicum strain of the present invention is obtained by mutating Corynebacterium glutamicum ATCC 13032, with the mutation sites including: mutating cytosine at site 862902 into thymine; mutating guanine at site 862903 into adenine; mutating cytosine at site 862953 into thymine; mutating adenine at site 862961 into guanine; inserting cytosine and thymine at site 862958; and mutating of guanine at site 862963 by deletion. The Corynebacterium glutamicum strain of the present invention exhibits significantly increased tolerance in high-viscosity environments and growth and metabolism ability under low dissolved oxygen conditions, thereby increasing the yield of mucopolysaccharides, and avoiding the problems where resulting mucopolysaccharides cause the fermentation broth to become viscous and have insufficient dissolved oxygen, which would further limit the metabolism of Corynebacterium glutamicum and ultimately affect the synthesis of mucopolysaccharides.