Nanoparticle mediated microvascular embolization (NME) of tumor tissue may occur after systemic administration of PEM as a result of the nitric oxide sequestration by PEM. Nitric oxide sequestration may cause a reduction in available extracellular nitric oxide in the tumor endothelium, which may prompt a widespread shutdown of vascular flow, hemorrhage, and necrosis. In particular, shutdown of vascular flow may trigger changes in nitric oxide production as well as trigger an acute inflammatory response, which may create reactive nitrogen species that are particularly destructive to the microvasculature. PEM constructs are developed that incorporate large amounts of iron-containing protein, possess high oxygen affinities, and demonstrate delayed nitric oxide binding. Such properties induce selective NME of tumors after extravasation, and will likely enhance the effect of VEGFR TKIs and/or mTOR inhibitors.

The present disclosure provides improved multiplex genome editing compositions and methods. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of a hemoglobinopathy, a cancer, an infectious disease, an autoimmune disease, an inflammatory disease, or an immunodeficiency.

Described herein are semisynthetic biopolymers comprising: a plurality of polyalkylene glycol chains, a protein, and an antioxidant; wherein the polyalkylene glycol chains are conjugated to the protein through a substituted succinimide linker. In some embodiments, the compounds described herein are conjugated proteins referred to as “semisynthetic supra perfusion agents”, “semisynthetic hybrid biopolymers”, “semisynthetic supra plasma expanders”, or the like. In some embodiments, these compounds mimic the same physiological consequences of high viscosity supra plasma expanders without being highly viscous—i.e. having a viscosity greater than blood.

Described herein are semisynthetic biopolymers comprising: a plurality of polyalkylene glycol chains, a protein, and an antioxidant; wherein the polyalkylene glycol chains are conjugated to the protein through a substituted succinimide linker. In some embodiments, the compounds described herein are conjugated proteins referred to as “semisynthetic supra perfusion agents”, “semisynthetic hybrid biopolymers”, “semisynthetic supra plasma expanders”, or the like. In some embodiments, these compounds mimic the same physiological consequences of high viscosity supra plasma expanders without being highly viscous—i.e. having a viscosity greater than blood.

Methods which increase the bioavailability of beneficial gases in the circulatory system are provided. The methods involve administering agents that changes the binding affinity of a medicinal gas such as NO, CO, H.sub.2S, N.sub.2O, SO, SO.sub.2 and O.sub.2 for IIb and/or hemoglobin based oxygen carriers (HBOCs). The change results in increased release of gases carried by Hb and HBOCs. As a result, the concentration of the gases in circulation is raised, and they are more available to exert their beneficial effects, e.g. in the treatment of disease or conditions caused by low levels of the gases. The methods are optionally used together with administration of medicinal gases and/or administration of HBOCs and/or other non-HBOC gas carriers such as PFC, and as (or in conjunction with) diagnostic methods.

Methods which increase the bioavailability of beneficial gases in the circulatory system are provided. The methods involve administering agents that changes the binding affinity of a medicinal gas such as NO, CO, H.sub.2S, N.sub.2O, SO, SO.sub.2 and O.sub.2 for IIb and/or hemoglobin based oxygen carriers (HBOCs). The change results in increased release of gases carried by Hb and HBOCs. As a result, the concentration of the gases in circulation is raised, and they are more available to exert their beneficial effects, e.g. in the treatment of disease or conditions caused by low levels of the gases. The methods are optionally used together with administration of medicinal gases and/or administration of HBOCs and/or other non-HBOC gas carriers such as PFC, and as (or in conjunction with) diagnostic methods.

Methods which increase the bioavailability of beneficial gases in the circulatory system are provided. The methods involve administering agents that changes the binding affinity of a medicinal gas such as NO, CO, H.sub.2S, N.sub.2O, SO, SO.sub.2 and O.sub.2 for IIb and/or hemoglobin based oxygen carriers (HBOCs). The change results in increased release of gases carried by Hb and HBOCs. As a result, the concentration of the gases in circulation is raised, and they are more available to exert their beneficial effects, e.g. in the treatment of disease or conditions caused by low levels of the gases. The methods are optionally used together with administration of medicinal gases and/or administration of HBOCs and/or other non-HBOC gas carriers such as PFC, and as (or in conjunction with) diagnostic methods.

The beta 2 subunit of mouse hemoglobin (HBB2) has been identified as soluble factor from mouse lungs that exhibits cytostatic/cytotoxic activity against neuroblastoma lung micrometastases. The beta subunit of human hemoglobin (HBB) has been found to have similar activity. Methods of using these proteins and fragments thereof in the treatment of cancer and inhibition of metastasis are provided, along with methods of screening a subject for micrometastases by detecting HBB in a biological sample.

The beta 2 subunit of mouse hemoglobin (HBB2) has been identified as soluble factor from mouse lungs that exhibits cytostatic/cytotoxic activity against neuroblastoma lung micrometastases. The beta subunit of human hemoglobin (HBB) has been found to have similar activity. Methods of using these proteins and fragments thereof in the treatment of cancer and inhibition of metastasis are provided, along with methods of screening a subject for micrometastases by detecting HBB in a biological sample.

The present invention provides compositions for the treatment of phenylketonuria in mammals, as well as methods of preparing said compositions. The present invention also provides methods of treating phenylketonuria using the compositions of the invention.