The present disclosure relates to pharmaceutical compositions comprising a non-naturally occurring fusion molecule and one or more pharmaceutically acceptable carriers, formulated for oral delivery to a subject, and designed to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases, autoimmune diseases, cancer, metabolic disorders, and growth deficiency disorders. The present disclosure relates to a non-toxic mutant form of the Vibrio cholera Cholix gene (ntCholix), a variant of Cholix truncated at amino acid A.sup.386 (Cholix.sup.386) and the use of other various Cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. The systems and methods described herein provide for: the ability to deliver macromolecule doses without injections; the ability to deliver cargo such as siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes.

The invention provides a method for treating acute myeloid leukemia (AML) in a subject in need thereof, said method comprising administering a therapeutically effective amount of an arginine-depleting agent to the subject, wherein the AML is of the French-American-British (FAB) subtype M0 (undifferentiated acute myeloblastic leukemia), M2 (acute myeloblastic leukemia with maturation), M4 (acute myeloblastic leukemia with maturation), M4 eos (acute myelomonocytic leukemia with eosinophilia), M5 (acute monocytic leukemia), M6 (acute erythroid leukemia) or M7 (acute megakaryoblastic leukemia).

The invention provides a method for treating acute myeloid leukemia (AML) in a subject in need thereof, said method comprising administering a therapeutically effective amount of an arginine-depleting agent to the subject, wherein the AML is of the French-American-British (FAB) subtype M0 (undifferentiated acute myeloblastic leukemia), M2 (acute myeloblastic leukemia with maturation), M4 (acute myeloblastic leukemia with maturation), M4 eos (acute myelomonocytic leukemia with eosinophilia), M5 (acute monocytic leukemia), M6 (acute erythroid leukemia) or M7 (acute megakaryoblastic leukemia).

Pharmaceutical compositions comprising spray-dried oxalate decarboxylase crystals are disclosed. Methods to treat a disorder associated with elevated oxalate concentration using compositions comprising spray-dried oxalate decarboxylase crystals are also disclosed.

Pharmaceutical compositions comprising spray-dried oxalate decarboxylase crystals are disclosed. Methods to treat a disorder associated with elevated oxalate concentration using compositions comprising spray-dried oxalate decarboxylase crystals are also disclosed.

Methods and compositions relating to the engineering of an improved protein with homocyst(e)inase enzyme activity are described. For example, there are disclosed modified cystathionine-γ-lyase (CGL) enzymes comprising one or more amino acid substitutions and capable of degrading homocyst(e)ine. Furthermore, provided are compositions and methods for the treatment of homocystinuria or hyperhomocysteinemia with homocyst(e)ine depletion using the disclosed enzymes or nucleic acids.

Methods and compositions relating to the engineering of an improved protein with homocyst(e)inase enzyme activity are described. For example, there are disclosed modified cystathionine-γ-lyase (CGL) enzymes comprising one or more amino acid substitutions and capable of degrading homocyst(e)ine. Furthermore, provided are compositions and methods for the treatment of homocystinuria or hyperhomocysteinemia with homocyst(e)ine depletion using the disclosed enzymes or nucleic acids.

The present invention relates to engineered extracellular vesicles (EVs) as a novel therapeutic approach to treating urea cycle disorders. More specifically, the invention relates to the use of various protein engineering and nucleic acid engineering strategies for improving loading of urea cycle proteins or nucleic acids encoding urea cycle proteins into EVs and targeting of the resultant EVs to tissues and organs of interest.

Embodiments of a composition and/or combination comprising an anionic dietary supplement and 25-hydroxy vitamin D are disclosed. The anionic dietary supplement may be a negative dietary cation anion difference (DCAD) supplement and/or may comprise magnesium chloride, magnesium sulfate, ammonium chloride, ammonium sulfate, and calcium sulfate, and/or complexes thereof. Also disclosed are embodiments of a method for administrating the combination and/or composition to an animal, such as a ruminant. In certain embodiments, the animal is a dairy cow, and the method may be a method for increasing milk yield, and/or improving the health of the animal.

Embodiments of a composition and/or combination comprising an anionic dietary supplement and 25-hydroxy vitamin D are disclosed. The anionic dietary supplement may be a negative dietary cation anion difference (DCAD) supplement and/or may comprise magnesium chloride, magnesium sulfate, ammonium chloride, ammonium sulfate, and calcium sulfate, and/or complexes thereof. Also disclosed are embodiments of a method for administrating the combination and/or composition to an animal, such as a ruminant. In certain embodiments, the animal is a dairy cow, and the method may be a method for increasing milk yield, and/or improving the health of the animal.