The present invention relates to variants of lysosomal acid lipase (LAL) and uses thereof.

A method for producing a protein encoded by a target gene, comprising the step of expressing the target gene in a bacterium of the genus Burkholderia, wherein the bacterium lacks one or more genes selected from the group consisting of BSFP_068740, BSFP_068730, and BSFP_068720, or has inhibited expression of the genes or proteins encoded by the genes.

The disclosure provides gene therapy vectors, such as adeno-associated virus (AAV), designed for treatment of Lysosomal Acid Lipase Deficiency (LAL-D) disorders such as Wolman Disease and cholesterol ester storage disease (CESD). The disclosed rAAV provide a wild type lipase A (LIRA) cDNA to a subject in need which results in expression of the wild type protein.

The present invention provides methods of treating LAL deficiency comprising administering to a mammal a therapeutically effective amount of lysosomal acid lipase with an effective dosage frequency. Methods of improving growth and river function, increasing LAL tissue concentration, and increasing LAL activity in a human patient suffering from LAL deficiency are also provided.

The present invention provides compositions of recombinant human lysosomal acid lipase having particular glycosylation patterns for internalization into target cells, a vector containing the nucleic acid encoding human lysosomal acid lipase, a host cell transformed with the vector, pharmaceutical compositions comprising the recombinant human lysosomal acid lipase and method of treating conditions associated with lysosomal acid lipase deficiency.

An apparatus and method of detecting components in a microfluidic sample. The sample and a plurality of microbeads are mixed within the microfluidic device. Each of the microbeads comprises a plurality of bioactive proteins bound thereon. A fluorescent signal is generated from a reaction of the microbeads and the microfluidic sample. The generated fluorescent signal is then able to be detected, wherein an intensity of fluorescence is directly proportional to a concentration of the peroxide generated.

Compositions and methods relating to potentially pathogenic mutations in the nucleotide sequence of a human LIPA gene. Some LIPA gene products have been discovered to be associated with reduced lysosomal acid lipase (LAL) activity.

The present invention comprises methods and compositions for the treatment or alleviation of NAFLD (non-alcoholic fatty liver disease) and those conditions associated with NAFLD, including fatty liver disease, nonalcoholic steatohepatitis (NASH) and cirrhosis through the use of pharmaceutical formulations of lysosomal acid lipase or related proteins and/or polypeptides. This invention is also directed to a combination therapy treatment for treating The Metabolic Syndrome. As part of a combination therapy regime for the treatment of The Metabolic Syndrome, pharmaceutical formulations of lysosomal acid lipase or related proteins and/or polypeptides are used as part of the combination therapy regime for treating NAFLD (and NASH), which comprises one of the conditions constituting The Metabolic Syndrome,

Detergent compositions that include a lipase variant of a parent lipase which has lipase activity and includes one or more substitutions corresponding to G23S, D27N, A40, F51I,L, E56R, D57N, V60E,K, K98I, N101D, R118, G163S, T231R, N233R, Y220F, T244E, and P256T using SEQ ID NO: 2 for numbering. Water-soluble unit dose articles including water-soluble film and a detergent composition including lipase variants. Methods of cleaning and/or treatment of surfaces using such compositions.

Detergent compositions that include a lipase variant of a parent lipase which has lipase activity and includes one or more substitutions corresponding to G23S, D27N, A40, F51I,L, E56R, D57N, V60E,K, K98I, N101D, R118, G163S, T231R, N233R, Y220F, T244E, and P256T using SEQ ID NO: 2 for numbering. Water-soluble unit dose articles including water-soluble film and a detergent composition including lipase variants. Methods of cleaning and/or treatment of surfaces using such compositions.