Cystic fibrosis (CF) is a common genetic disease that affects the entire body, producing thick, sticky mucus that clogs the lungs, pancreas, and other organs. It is the most common fatal genetic disease in the United States, and is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR).

Podocytes, cells of the visceral epithelium in the kidneys, are a key component of the glomerular filtration barrier. As such, they play a vital role in glomerular disorders, which are a major cause of chronic kidney disease. Examples of these disorders include focal segmental glomerulosclerosis, membranous glomerulonephritis, minimal change disease, and diabetic nephropathy.

Serotonin is an important modulator of many developmental, behavioral, and physiological processes, and it has been implicated in depression, anxiety, schizophrenia, obsessive compulsive disorders, and substance abuse. Serotonin’s pharmacology is extremely complex and it is mediated by seven of serotonin receptor subtypes and it is present in several tissues. Although it has been a subject of a number of studies, its role has been difficult to ascertain. To investigate the role of serotonin in these disorders, the murine gene was disrupted by homologous recombination.

Calcium is a key element in the regulation of many cellular processes, including muscle contraction, hormone excretion from gland cells, neurotransmitter release from nerve synapses, and the regulation of cellular metabolism. Elevated calcium levels are found in a number of diseases.

Human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT) gene encodes 560 amino acids. In the virus, however, HIV-1 RT occurs as a dimer of two related polypeptides, p66 and p51 subunits at a molar ratio of 1:1. The p51 subunit is derived from a C-terminal proteolytic cleavage of the p66 subunit. This invention describes a simplified protocol to purify large quantities of histidine-tagged and untagged heterodimeric forms of human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT) from Escherichia coli.

Autoimmune inflammatory diseases occur in greater than five percent of the United States population; this disease group includes asthma, multiple sclerosis, rheumatoid arthritis, and lupus. Treatments generally include immunosuppressants or anti-inflammatory drugs, which can have serious side effects; recently, more specific immunomodulatory therapies such as TNF-alpha antagonists have been developed.

Gene therapy and gene transfer have recently been recognized as effective therapeutic tools to combat diseases. Accordingly, market demands for vectors and carriers to facilitate such interventions have surged in recent years. Retroviral vectors provide an efficient and safe means of gene transfer to eukaryotic cells. The present invention relates to genetic engineering involving retrovirus packaging cells that produce retroviral vectors.

The invention concerns immunotoxins and methods of using the immunotoxins for the treatment of autoimmune diseases and T cell malignancies. The immunotoxins are targeted via an antibody that is specific to T cells. This allows the specific ablation of malignant T cells and resting T cells. The transient ablation of resting T cells can "reset" the immune system by accentuating tolerizing responses. The toxin portion of the immunotoxin is genetically engineered to maintain bioactivity when recombinantly produced in Pichia pastoris.

The invention concerns immunotoxins and methods of using the immunotoxins for the treatment of rejection response in a patient, including graft-versus-host disease and transplantation of organs, tissues and cells into a host. In a specific embodiment of the invention, the transplant involves pancreatic islet cells. The immunotoxins are targeted via an antibody that is specific to T cells. This allows the specific ablation of resting T cells, resulting in an accentuation of immune tolerizing responses and an increased tolerance to transplants and grafts.

The invention concerns immunotoxins and methods of making the immunotoxins. Targeting of the immunotoxins occurs via an antibody that is specific to T cells. This allows the specific ablation of malignant T cells and resting T cells. The transient ablation of resting T cells can "reset" the immune system by accentuating tolerizing responses. As a result, the immunotoxin can be used to treat autoimmune disease, malignant T cell-related cancers, and graft-versus-host disease.