The present invention comprises a method of concentrating a composition comprising a polypeptide of interest and the use of such concentrated composition for the treatment of diseases in mammals, in particular by subcutaneous injection.

The present invention comprises a method of concentrating a composition comprising a polypeptide of interest and the use of such concentrated composition for the treatment of diseases in mammals, in particular by subcutaneous injection.

The present invention comprises a method of concentrating a composition comprising a polypeptide of interest and the use of such a concentrated composition for the treatment of diseases in mammals, in particular by subcutaneous injection.

The invention relates to mRNA therapy for the treatment of Acute Intermittent Porphyria (AIP). mRNAs for use in the invention, when administered in vivo, encode human porphobilinogen deaminase (PBGD), isoforms thereof, functional fragments thereof, and fusion proteins comprising PBGD. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to affect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of PBGD expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient PBGD activity in subjects, namely porphobilinogen and aminolevulinate (PBG and ALA).

Provided is a chimeric transcriptional activator for a methanol-inducible promoter, which at least comprises a first portion and a second portion, wherein: 1) the first portion comprises: i) a DNA binding domain; or ii) a DNA binding domain and a first transcription activation domain; and 2) the second portion comprises at least one second transcription activation domain. Further provided is a use of the chimeric transcriptional activator in enhancing foreign protein expression levels in a host cell.

A genetically modified yeast cell, wherein the yeast cell comprises a genetic modification comprising overexpression of yeast gene encoding porphobilinogen deaminase (HEM3), the HEM3 gene having at least 80% identity with SEQ ID No. 7. The genome of the modified yeast cell further comprises one or more genetic modifications in one or more genes selected from: genes coding for heme-dependent repressor of hypoxic genes (ROX1), genes coding for heme oxygenase (HMX1), genes coding for a receptor for vacuolar proteases (VPS10), and genes coding for vacuolar proteinase (PEP4), the one or more genetic modifications being such that expression of a polypeptide from such a gene is reduced or disrupted or the polypeptide expressed is non-functional.

Plants and plant tissue such as leaves comprising leghemoglobin are produced by modifying the genome of the plant or introducing leghemoglobin coding or regulatory sequences into the plant. Plants, leaves, fruits, tubers, roots, seeds, and protein compositions comprising leghemoglobin are provided. Protein compositions comprising leghemoglobin, such as isolates and concentrates, can be made from the plants, tissue, fruits, tubers, roots, seeds and leaves. Additionally, methods for generating and using plants, tissue, fruits, tubers, roots, seeds, leaves and protein compositions comprising leghemoglobin are disclosed.