The present invention relates to a medicament comprising an arginine decomposing enzyme, and a citrulline converting enzyme useful for the treatment of cancer.

Processes and compositions for the therapeutic treatment of pathogenic Gram-negative bacterial infection are provided whereby argininosuccinate synthetase or PEGylated argininosuccinate synthetase is administered to a subject to inactivate endotoxin thereby reducing the likelihood of bacterial sepsis and improving patient outcome.

Processes and compositions for the therapeutic treatment of pathogenic Gram-negative bacterial infection are provided whereby arginino succinate synthetase or PEGylated arginino succinate synthetase is administered to a subject to inactivate endotoxin thereby reducing the likelihood of bacterial sepsis and improving patient outcome.

A microorganism produces guanidinoacetic acid (GAA) and has at least one gene coding for a protein having the function of a NADH-dependent dehydrogenase. A method for the fermentative production of GAA uses such microorganism. A method produces creatine through fermentative production. Industrial feed stocks are used as starting material in the fermentative process.

A microorganism is transformed to be capable of producing guanidinoacetic acid (GAA). A method can be used for the fermentative production of GAA using such microorganism. A corresponding method can also be used for the fermentative production of creatine.

Compositions and regimens useful in treating type I citrullenemia are provided. The compositions include recombinant adeno-associated virus (rAAV) with a transthyretin enhancer and promoter driving expression of a human Argininosuccinate Synthase 1 (ASS1).

A microorganism is transformed to be capable of producing guanidinoacetic acid (GAA) having an inactivated amino acid exporter. The microorganism is used in a method for the fermentative production of GAA. Moreover, creatine is produced by a method of fermentative production.

Nucleic acid constructs and compositions that allow insertion of an argininosuccinate synthase 1 (ASS1) coding sequence into a target genomic locus such as an endogenous ASS1 locus and/or expression of the ASS1 coding sequence are provided. Also provided are nuclease agents (e.g., targeting an endogenous ASS1 locus) or nucleic acids encoding nuclease agents to facilitate integration of the nucleic acid constructs into a target genomic locus such as an endogenous ASS1 locus. The nucleic acid constructs and compositions can be used in methods of introducing an ASS1 nucleic acid into a cell, methods of integration of an ASS1 nucleic acid into a target genomic locus, methods of expression of ASS1 in a cell, and in methods of treating citrullinemia type I or ASS1 deficiency in a subject.

The present invention provides, among other things, methods of treating Argininosuccinate Synthetase Deficiency (ASD), including administering to a subject in need of treatment a composition comprising an mRNA encoding argininosuccinate synthetase (ASS1) at an effective dose and an administration interval such that at least one symptom or feature of ASD is reduced in intensity, severity, or frequency or has delayed in onset. In some embodiments, the mRNA is encapsulated in a liposome comprising one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids.

Genetically engineered immune cells, which express at least two metabolism modulating polypeptides and optionally a chimeric receptor polypeptide (e.g., an antibody-coupled T cell receptor (ACTR) polypeptide or a chimeric antigen receptor (CAR) polypeptide) capable of binding to a target antigen of interest. Also disclosed herein are uses of the engineered immune cells for inhibiting cells expressing a target antigen in a subject in need thereof.