The present invention provides an improved process for lipid nanoparticle formulation and mRNA encapsulation. In some embodiments, the present invention provides a process of encapsulating messenger RNA (mRNA) in lipid nanoparticles comprising a step of mixing a suspension of preformed lipid nanoparticles and mRNA.

Provided are fusion target-binding proteins comprising a target binding moiety, an intracellular signalling region and a domain that promotes synthesis of arginine or an arginine precursor. The domain may be an enzyme domain such as an argininosuccinate synthase (ASS-1) enzyme domain, or an ornithine transcarbamylase (OTC) enzyme domain. Also provided are cells comprising such a fusion target-binding protein (for example cells that express the fusion target-binding protein), and nucleic acids encoding such fusion target-binding proteins. The invention also provides fusion target-binding proteins comprising a target binding moiety, an intracellular signalling region and a domain that promotes synthesis of tryptophan or a tryptophan precursor. Pharmaceutical compositions, medical uses, and methods of treatment, all using the fusion target-binding proteins, cells, or nucleic acids are disclosed. The proteins, cells, nucleic acids and pharmaceutical compositions may be used in the prevention and/or treatment of cancer, such as neuroblastoma or acute myeloid leukaemia.

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.

Provided herein are methods for facilitating or inducing stable transgene integration and expression in a proliferating cell, comprising administering to the cell (i) a recombinant AAV (rAAV) vector comprising the transgene flanked by transposon-derived inverted terminal repeat sequences, which sequences are in turn flanked by AAV-derived inverted terminal repeat regions, and (ii) a source of a transposase that recognises said transposon-derived inverted terminal repeat sequences and directs the genomic integration of the transgene into the genome of the proliferating cell. Also provide are methods and transgene delivery systems for the treatment or prevention of diseases affecting, associated with or characterised by proliferating cells.

The present invention provides an improved process for lipid nanoparticle formulation and mRNA encapsulation. In some embodiments, the present invention provides a process of encapsulating messenger RNA (mRNA) in lipid nanoparticles comprising a step of mixing a solution of pre-formed lipid nanoparticles and mRNA.

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). A method can be used for the fermentative production of GAA using such a microorganism. A corresponding method can be used for the fermentative production of creatine.

A replication-competent recombinant virus includes an expression cassette encoding a protein associated with arginine biosynthesis. The protein associated with arginine biosynthesis may include argininosuccinate synthase 1 (ASS1), argininosuccinate lyase (ASL), or ornithine transcarboxylase (OTC). The recombinant virus may be derived from a myxoma virus. A method of treating a cell includes contacting a cell with a recombinant virus including an expression cassette encoding a protein associated with arginine biosynthesis. The protein associated with arginine biosynthesis may be ASS1, ASL, OTC.

The present invention provides an improved process for lipid nanoparticle formulation and mRNA encapsulation. In some embodiments, the present invention provides a process of encapsulating messenger RNA (mRNA) in lipid nanoparticles comprising a step of mixing a solution of pre-formed lipid nanoparticles and mRNA.

The present invention provides an improved process for lipid nanoparticle formulation and mRNA encapsulation. In some embodiments, the present invention provides a process of encapsulating messenger RNA (mRNA) in lipid nanoparticles comprising a step of mixing a suspension of preformed lipid nanoparticles and mRNA.