Described herein are heme-binding compositions and methods relating to their use, for example methods of treatment of sepsis and rhabdomyolysis.

The present invention provides AAV capsid proteins comprising modification of one or a combination of the surface-exposed lysine, serine, threonine and/or tyrosine residues in the VP3 region. Also provided are rAAV virions comprising the AAV capsid proteins of the present invention, as well as nucleic acid molecules and rAAV vectors encoding the AAV capsid proteins of the present invention. Advantageously, the rAAV vectors and virions of the present invention have improved efficiency in transduction of a variety of cells, tissues and organs of interest, when compared to wild-type rAAV vectors and virions.

The present invention provides a pharmaceutical composition containing recombinant hemoglobin protein or tetramer or dimer or subunit for tissue oxygenation and treating cancer. The recombinant hemoglobin protein or tetramer or dimer or subunit-based therapeutic agent is also effective for treating cancer. The recombinant hemoglobin or tetramer or dimer or its subunit moiety can target cancer cells and the therapeutic moiety (i.e. active agent/therapeutic drug) can kill the cancer cells efficiently. The recombinant hemoglobin or tetramer or dimer or its subunit-based therapeutic agent used in the present invention can be used in the treatment of various cancers such as pancreatic cancer, leukemia, head and neck cancer, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal cancer, esophageal cancer, prostate cancer, stomach cancer and brain cancer. The composition can be used alone or in combination with other therapeutic agent(s) such as chemotherapeutic agent, radiotherapeutic agent, anti-cancer protein drug to give a synergistic effect on cancer treatment, inhibiting metastasis and/or reducing recurrence.

The present invention provides a pharmaceutical composition containing recombinant hemoglobin protein or tetramer or dimer or subunit for tissue oxygenation and treating cancer. The recombinant hemoglobin protein or tetramer or dimer or subunit-based therapeutic agent is also effective for treating cancer. The recombinant hemoglobin or tetramer or dimer or its subunit moiety can target cancer cells and the therapeutic moiety (i.e. active agent/therapeutic drug) can kill the cancer cells efficiently. The recombinant hemoglobin or tetramer or dimer or its subunit-based therapeutic agent used in the present invention can be used in the treatment of various cancers such as pancreatic cancer, leukemia, head and neck cancer, colorectal cancer, lung cancer, breast cancer, liver cancer, nasopharyngeal cancer, esophageal cancer, prostate cancer, stomach cancer and brain cancer. The composition can be used alone or in combination with other therapeutic agent(s) such as chemotherapeutic agent, radiotherapeutic agent, anti-cancer protein drug to give a synergistic effect on cancer treatment, inhibiting metastasis and/or reducing recurrence.

The invention relates to hemoglobin derivative, particularly hemoglobin which is co-conjugated with both fatty acid-linked polyethylene glycol (FA-PEG) derivatives and alkoxy polyethylene glycol (alkoxy-PEG) derivatives, and a method for making such hemoglobin derivative. Various embodiments of the invention include crosslinked hemoglobin which is co-conjugated with both FA-PEG derivatives and alkoxy-PEG derivatives. Such hemoglobin derivative according to the invention exhibit non-toxicity and extended intravascular retention time.

An object of the present invention is to provide a novel preservative solution for a heme protein and a method for stabilizing a heme protein, which are effective against denaturation or degradation of a heme protein, and the present invention specifically relates to a preservative solution for a heme protein comprising a disulfonic acid or a salt thereof, and a method for stabilizing a heme protein, which involves bringing a disulfonic acid or a salt thereof into coexistence in a sample comprising a heme protein.

An object of the present invention is to provide a novel preservative solution for a heme protein and a method for stabilizing a heme protein, which are effective against denaturation or degradation of a heme protein, and the present invention specifically relates to a preservative solution for a heme protein comprising a disulfonic acid or a salt thereof, and a method for stabilizing a heme protein, which involves bringing a disulfonic acid or a salt thereof into coexistence in a sample comprising a heme protein.

Synthetic heme-containing molecules are described. The heme-containing molecules include a heme group bound to either two non-contiguous peptides or a single contiguous peptide via cysteine residues. Use of the synthetic heme-containing molecules, such as for the treatment of carboxyhemoglobinemia, cyanide poisoning and hydrogen sulfide (H.sub.2S) poisoning, is further described.

Synthetic heme-containing molecules are described. The heme-containing molecules include a heme group bound to either two non-contiguous peptides or a single contiguous peptide via cysteine residues. Use of the synthetic heme-containing molecules, such as for the treatment of carboxyhemoglobinemia, cyanide poisoning and hydrogen sulfide (H.sub.2S) poisoning, is further described.

In certain aspects, the present invention provides methods for inducing a stable gene modification of a target nucleic acid via homologous recombination in a primary cell, such as a primary blood cell and/or a primary mesenchymal cell. In certain other aspects, the present invention provides methods for enriching a population of genetically modified primary cells having targeted integration at a target nucleic acid. The methods of the present invention rely on the introduction of a DNA nuclease such as a Cas polypeptide and a homologous donor adeno-associated viral (AAV) vector into the primary cell to mediate targeted integration of the target nucleic acid. Also provided herein are methods for preventing or treating a disease in a subject in need thereof by administering to the subject any of the genetically modified primary cells or pharmaceutical compositions described herein to prevent the disease or ameliorate one or more symptoms of the disease.