The present disclosure provides methods and compositions for transferring a gene encoding sphingosine-1-phosphate lyase (SPL) in a subject in need thereof by using recombinant AAV virions. The subject may have or may develop SPL insufficiency syndrome (SPLIS). The subject may be identified on the basis of a genetic test and/or SPLIS symptoms. The methods and compositions are also useful in lowering circulating sphingosine-1-phosphate levels in a subject having elevated S1P levels.

The present invention relates to compounds and methods for the prevention or treatment of infections by negative strand RNA viruses, such as influenza virus and measles virus, wherein said compounds delay or inhibit viral replication by modulating the level or activity of a polypeptide involved in the synthesis or degradation of sphingosine-1-phosphate (S1P) in a cell, tissue, or subject. The methods involve administration of one or more compounds which modulate the level of gene expression, where the gene encodes a polypeptide involved in regulating the metabolic level of S1P, or modulate the level or activity of a polypeptide involved in regulating the metabolic level of S1P, such as sphingosine kinase (SK) and S1P lyase (SPL). Exemplary methods are directed towards reducing the level of SW by reducing the level or activity of one or more SKs, increasing the level or activity of one or more SPLs, or a combination of both steps.

The invention relates to genetically modified Pichia ciferrii cells, to the use thereof and to a method of producing sphingoid bases and sphingolipids.

The present disclosure provides methods treating or preventing pulmonary fibrosis in a subject in need thereof by administering to the subject a therapeutically effective dose of a recombinant adeno-associated viral (rAAV) virion comprising a nucleic acid encoding sphingosine-1-phosphate lyase (SPL), where administering the rAAV virion results in expression of the SPL in the subject thereby treating or preventing the pulmonary fibrosis in the subject.