The invention provides a composition for use as a medicament, comprising cells of a recombinant microorganism capable of producing increased amounts of one or more of 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT) and tryptamine (TRM) as compared to the non-recombinant microorganism from which it was derived. The composition finds use in preventing and/or treating TRM-; 5-HTP-, or 5-HT-related disorders of the central nerve system (CNS); enteric nervous system (ENS); gastro intestine (GI) and metabolism in a mammal, and may be orally administered to a mammal in need thereof. Additionally, a composition comprising cells of a recombinant microorganism capable of producing melatonin is provided for use as a medicament, such as for treatment of depression, dementia, cancer and sleep disorder.

The invention provides a composition for use as a medicament, comprising cells of a recombinant microorganism capable of producing increased amounts of one or more of 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT) and tryptamine (TRM) as compared to the non-recombinant microorganism from which it was derived. The composition finds use in preventing and/or treating TRM-; 5-HTP-, or 5-HT-related disorders of the central nerve system (CNS); enteric nervous system (ENS); gastro intestine (GI) and metabolism in a mammal, and may be orally administered to a mammal in need thereof. Additionally, a composition comprising cells of a recombinant microorganism capable of producing melatonin is provided for use as a medicament, such as for treatment of depression, dementia, cancer and sleep disorder.

Genetically modified proteins with uricolytic activity are described. Proteins comprising truncated urate oxidases and methods for producing them, including PEGylated proteins comprising truncated urate oxidase are described.

Genetically modified proteins with uricolytic activity are described. Proteins comprising truncated urate oxidases and methods for producing them, including PEGylated proteins comprising truncated urate oxidase are described.

Provided are compositions related to HSD17B13 variants, including isolated nucleic acids and proteins related to variants of HSD17B13, and cells comprising those nucleic acids and proteins. Also provided are methods related to HSD17B13 variants. Such methods include methods for modifying a cell through use of any combination of nuclease agents, exogenous donor sequences, transcriptional activators, transcriptional repressors, and expression vectors for expressing a recombinant HSD17B13 gene or a nucleic acid encoding an HSD17B13 protein. Also provided are therapeutic and prophylactic methods for treating a subject having or at risk of developing chronic liver disease.

Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of muscle cells as compared to the infectivity of the muscle cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and in clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more muscle cells for the treatment of muscle disorders and diseases.

Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of muscle cells as compared to the infectivity of the muscle cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and in clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more muscle cells for the treatment of muscle disorders and diseases.

The present disclosure generally relates to methods and formulations for treating central nervous system (CNS) disorders. The present disclosure involves intranasal delivery of at least one antioxidant compound, allowing for effective treatment of a central nervous system disorder such as traumatic brain injury or stroke.

Methods of reactivating latent human immunodeficiency virus (HIV) in one or more cells of a patient infected with HIV are provided. Methods of treating HIV infection and acquired immune deficiency syndrome (HIV/AIDS) in a patient are also provided. The methods can include administering a crotonylation-inducing agent to the patient. The methods can also include administering a crotonylation-inducing agent and one or more additional latency reversal agents (LRAs) to the patient. Pharmaceutical compositions including a crotonylation-inducing agent or pharmaceutical compositions including a crotonylation-inducing agent and one or more additional LRAs are also provided.

Methods of reactivating latent human immunodeficiency virus (HIV) in one or more cells of a patient infected with HIV are provided. Methods of treating HIV infection and acquired immune deficiency syndrome (HIV/AIDS) in a patient are also provided. The methods can include administering a crotonylation-inducing agent to the patient. The methods can also include administering a crotonylation-inducing agent and one or more additional latency reversal agents (LRAs) to the patient. Pharmaceutical compositions including a crotonylation-inducing agent or pharmaceutical compositions including a crotonylation-inducing agent and one or more additional LRAs are also provided.