Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a metabolic disorder of the liver that results m abnormal nitrogen metabolism. To illustrate the ability of gene therapy to treat CPS1 deficiency, two adeno-associated viruses encoding portions of a codon optimized CPS1 were generated and tested in a conditional CPS1 knock out mouse model. When administered to mice having knocked out endogenous CPS1 expression, mice from this model demonstrate homologous recombination and reconstitution of the codon optimized CPS1 gene, expression of the CPS1 protein and the associated control of plasma ammonia following the administered AAVs comprising the CPS1 gene sequences. While all control mice perish, the mice in this model live and have normal behavior. As there is no effective therapy for human patients with the CPS1 disorder, this invention can address this unmet need for these patients.

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.

Described herein are methods of modulating gene transcription using antisense oligonucleotides (ASOs) targeting regulatory RNAs, such as promoter-associated RNAs and enhancer RNAs. These methods are useful for modulating the levels of gene products, for example, increasing expression of Carbamoyl-Phosphatase Synthetase 1 (CPS1), thereby treating diseases associated with aberrant gene expression.

Provided are a microorganism producing L-amino acids, in which activity of carbamoyl phosphate synthetase is weakened, and a method of producing L-amino acids using the same.

Described herein are methods of modulating gene transcription using antisense oligonucleotides (ASOs) targeting regulatory RNAs, such as promoter-associated RNAs and enhancer RNAs. These methods are useful for modulating the levels of gene products, for example, increasing expression of Carbamoyl-Phosphatase Synthetase 1 (CPS1), thereby treating diseases associated with aberrant gene expression.

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.

Disclosed are gene engineering bacteria for producing L-arginine and a construction method and an application of the gene engineering bacteria. According to the method, genes encoding a carbamoyl phosphate synthetase and a gene encoding an L-arginine biosynthesis pathway enzyme are integrated into Escherichia coli; the present invention has analyzed and reconstructed the arginine synthetic pathway and the metabolic flow related to arginine in the entire amino acid metabolic network in E. coli and finally obtained a genetically engineered bacterial strain which has a clear genetic background, carries no plasmids, undergoes no mutagenesis and is capable of stably and efficiently producing L-arginine.