ADP-ribosylation is important in many cellular processes, including DNA replication and repair, maintenance of genomic stability, telomere dynamics, cell differentiation and proliferation, and necrosis and apoptosis. Poly-ADP-ribose is important in a number of critical physiological processes such as DNA repair, cellular differentiation, and carcinogenesis. Until recently, only one human enzyme, PARG, had been identified that degrades the ADP-ribose polymer.

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).

Reactivation of latent Varicella-Zoster virus (VZV) infection is the cause of shingles, which is prominent in adults over the age of 60 and individuals who have compromised immune systems, due to HIV infection, cancer treatment and/or transplant. Shingles is a worldwide health concern that affects approximately 600,000 Americans each year. The incidence of shingles is also high in Europe, South America, and India; the latter having an estimated two million individuals affected, yearly.

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.

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.

This technology identifies twenty five (25) new alternatively spliced transcripts of the BORIS gene. The transcripts lead to the expression of seventeen different protein isoforms with variable N- and C-termini encoded by BORIS gene locus. Differential expression levels of BORIS isoforms were observed in different cancers. While some BORIS alternative splice variants were expressed at different levels in all types of cancers, other expressed forms are specific to particular cancer(s).

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.