The present disclosure provides engineered human extracellular DNASE proteins (e.g., variants of DNASE1 (D1), DNASE1-LIKE 1 (D1L1), DNASE1-LIKE 2 (DTL2), DNASE1-LIKE 3 Isoform 1 (DTL3), DNASE1-LIKE 3 Isoform 2 (DTL3-2), DNASE2A (D2A), and DNASE2B (D2B)) that are useful for treating conditions characterized by neutrophil extracellular trap (NET) accumulation and/or release. In accordance with the invention, the DNase variant has advantages for therapy and/or large-scale manufacturing.

The present disclosure provides engineered human extracellular DNASE proteins (e.g., variants of DNASE1 (D1), DNASE1-LIKE 1 (D1L1), DNASE1-LIKE 2 (DTL2), DNASE1-LIKE 3 Isoform 1 (DTL3), DNASE1-LIKE 3 Isoform 2 (DTL3-2), DNASE2A (D2A), and DNASE2B (D2B)) that are useful for treating conditions characterized by neutrophil extracellular trap (NET) accumulation and/or release. In accordance with the invention, the DNase variant has advantages for therapy and/or large-scale manufacturing.

The present invention provides fusion proteins comprising leptin and a second protein. The presence of the second protein provides increased biological activity and/or increased half-life in vivo. The present invention also provides human, canine and feline leptin molecules fused to peptides, antibodies or antibody fragments which enhances the abilities of the leptin molecules to transport through the blood-brain-barrier (BBB). The present invention also provides fusion proteins further comprising a peptide agonist that is capable of binding to and stimulate one, two or all three of the following receptors: GLP-1 receptor, Glucagon receptor, and GIP receptor. Also disclosed is a method of production such fusion proteins through recombinant technologies. The invention further discloses a pharmaceutical composition comprising one of the fusion proteins as an active intergradient as well as a method for using such a pharmaceutical composition to treat diseases in dogs, cats and humans.

The present invention provides fusion proteins comprising leptin and a second protein. The presence of the second protein provides increased biological activity and/or increased half-life in vivo. The present invention also provides human, canine and feline leptin molecules fused to peptides, antibodies or antibody fragments which enhances the abilities of the leptin molecules to transport through the blood-brain-barrier (BBB). The present invention also provides fusion proteins further comprising a peptide agonist that is capable of binding to and stimulate one, two or all three of the following receptors: GLP-1 receptor, Glucagon receptor, and GIP receptor. Also disclosed is a method of production such fusion proteins through recombinant technologies. The invention further discloses a pharmaceutical composition comprising one of the fusion proteins as an active intergradient as well as a method for using such a pharmaceutical composition to treat diseases in dogs, cats and humans.

Provided herein are compositions and methods to make and use engineered cells, for the purpose of increasing the cell density of a culture comprising metazoan cells and for the production of a cultured edible product.

Provided herein are compositions and methods to make and use engineered cells, for the purpose of increasing the cell density of a culture comprising metazoan cells and for the production of a cultured edible product.

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized albumin (ALB) locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized albumin locus express a human albumin protein or a chimeric albumin protein, fragments of which are from human albumin. Methods are provided for using such non-human animals comprising a humanized albumin locus to assess in vivo efficacy of human-albumin-targeting reagents such as nuclease agents designed to target human albumin.

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized albumin (ALB) locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized albumin locus express a human albumin protein or a chimeric albumin protein, fragments of which are from human albumin. Methods are provided for using such non-human animals comprising a humanized albumin locus to assess in vivo efficacy of human-albumin-targeting reagents such as nuclease agents designed to target human albumin.

Provided herein are compositions and methods to make and use engineered cells, for the purpose of increasing the cell density of a culture comprising metazoan cells and for the production of a cultured edible product.

Provided herein are compositions and methods to make and use engineered cells, for the purpose of increasing the cell density of a culture comprising metazoan cells and for the production of a cultured edible product.