A non-naturally occurring cell comprising an inoperative genomic asparaginase (Aspg) gene and an inoperative glutamine synthetase (Gs) gene, wherein the cell has been transfected with a controllably expressed gene encoding an enzyme having asparaginase activity, a controllably expressed gene encoding an enzyme having glutamine synthetase activity, and a controllably expressed gene encoding a heterologous protein of interest.

Peptides that specifically bind erythrocytes are described. These are provided as peptidic ligands having sequences that specifically bind, or as antibodies or fragments thereof that provide specific binding, to erythrocytes. The peptides may be prepared as molecular fusions with therapeutic agents, tolerizing antigens, or targeting peptides. Immunotolerance may be created by use of the fusions and choice of an antigen on a substance for which tolerance is desired.

Peptides that specifically bind erythrocytes are described. These are provided as peptidic ligands having sequences that specifically bind, or as antibodies or fragments thereof that provide specific binding, to erythrocytes. The peptides may be prepared as molecular fusions with therapeutic agents, tolerizing antigens, or targeting peptides. Immunotolerance may be created by use of the fusions and choice of an antigen on a substance for which tolerance is desired.

The present invention relates to asparaginase variants. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants. The invention further relates to a process of producing a fermentation product, comprising: liquefying a starch-containing material to dextrins with an alpha-amylase in the presence of an asparaginase of the invention; saccharifying the dextrins to a sugar with a glucoamylase; and fermenting the sugar using a fermenting organism.

The present invention relates to asparaginase variants. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants. The invention further relates to a process of producing a fermentation product, comprising: liquefying a starch-containing material to dextrins with an alpha-amylase in the presence of an asparaginase of the invention; saccharifying the dextrins to a sugar with a glucoamylase; and fermenting the sugar using a fermenting organism.

The invention relates to methods of treating diseases with L-asparaginase.

The disclosure provides a modified protein that is a combination of (i) an L-asparaginase and (ii) one or more (poly)peptide(s), wherein the (poly)peptide consists solely of proline and alanine amino acid residues, and methods of preparation and use thereof.

The disclosure provides a modified protein that is a combination of (i) an L-asparaginase and (ii) one or more (poly)peptide(s), wherein the (poly)peptide consists solely of proline and alanine amino acid residues, and methods of preparation and use thereof.

Methods of treating cancer and prolonging survival of a subject having cancer, such as acute myeloid leukemia, via administration of therapeutically effective amounts of agents that depletes plasma glutamine and agents that inhibit BCL-2 activity are detailed herein. Suitable agents that depletes plasma glutamine include asparaginase Suitable agents that inhibit BCL-2 activity include Venetoclax.

Methods of treating cancer and prolonging survival of a subject having cancer, such as acute myeloid leukemia, via administration of therapeutically effective amounts of agents that depletes plasma glutamine and agents that inhibit BCL-2 activity are detailed herein. Suitable agents that depletes plasma glutamine include asparaginase Suitable agents that inhibit BCL-2 activity include Venetoclax.