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.

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.

The present disclosure describes compositions and methods for treating ornithine transcarbamylase (OTC) deficiency. The compositions include a lipid formulation and messenger RNA (mRNA) encoding an OTC enzyme. The lipid formulations can comprise an ionizable cationic lipid in a lipid nanoparticle encapsulating the mRNA.

Disclosed are cationic polymers comprising monomers such as those described in Formula (I), ##STR00001## Such polymers can be useful for the preparation of therapeutic compositions (e.g., compositions comprising nucleic acids such as mRNA). Additionally, therapeutic compositions comprising these cationic, biodegradable polymers can have improved properties and reduced toxicity.

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.

The present disclosure provides a modified human OTC protein having improved properties for the treatment of OTC deficiency in a patient. Preferably, the protein of the disclosure is produced from a codon optimized mRNA suitable for administration to a patient suffering from OTC deficiency wherein upon administration of the mRNA to the patient, the protein of the disclosure is expressed in the patient in therapeutically effective amounts to treat OTC deficiency. The present disclosure also provides codon optimized mRNA sequences encoding wild type human OTC comprising a 5 UTR derived from a gene expressed by Arabidopsis thaliana for use in treating OTC deficiency in a patient.

The present invention relates, in part, to methods for large-scale purification of mRNA. The method includes, at least, a step of centrifuging an mRNA suspension in a centrifuge comprising a porous substrate at a speed sufficient to remove process contaminants and to precipitate purified mRNA composition onto the porous substrate.

Provided herein are compositions and methods for facilitating or enhancing delivery of nucleic acids, such as synthetic mRNAs, into cells or tissues. Such compositions and methods may include use of a targeting moiety-conjugated, such as an N-acetylgalactosamine (GalNAc)-conjugated, oligonucleotide to facilitate or enhance delivery.

Provided are a microorganism having L-ornithine-producing ability and a method of producing L-ornithine using the same.

The present application provides a novel means for treating ornithine transcarbamylase deficiency. More specifically, the present application provides a modified adeno-associated virus vector which expresses ornithine transcarbamylase so that an attack from a neutralizing antibody in blood is reduced and a gene is efficiently introduced into a liver of a living body (for example, human). The present application provides, for example, a modified adeno-associated virus vector which expresses omithine transcarbamylase, which contains a modified VP1 protein that contains, for example, an amino acid sequence obtained by substituting at least one of the amino acids at positions 472, 587 and 706 in the amino acid sequence of the VP1 protein with another amino acid, and which does not cross-react with a neutralizing antibody against AAV2.