Method of Producing Immortalized Primary Human Keratinocytes for HPV Investigation, Testing of Therapeutics, and Skin Graft Generation

One of the major limitations of using cultured keratinocytes for research studies is that primary keratinocytes senesce after a few passages. Keratinocytes from specific anatomical sites are also difficult to culture. Scientists at the NIH have demonstrated that primary keratinocytes, from several anatomical sites, when treated with a small-molecule inhibitor of the ROCK protein maintain a proliferative state and become immortal without genetic modification to the cells.

Full-Length Infectious cDNA Clones of Tick Borne Flavivirus

The tick-borne encephalitis virus complex of flavivirus family includes tick-borne encephalitis (TBEV), Kyasanur forest disease, Langat, Louping ill, Negishi, Omsk hemorrhagic fever and Povassan viruses. These viruses are endemic throughout most of the Northern Hemisphere and except for Langat, cause human disease of varying severity that can have mortality as high as 20 to 30%.

Prevention and Treatment of Herpes Virus Infection by Inhibition of the JMJD2 Family of Histone Demethylases

Investigators at the NIH have discovered a potential means for preventing or treating a herpes virus infection by inhibiting the activity of the host cell’s histone demethylases. When herpesviruses enter a cell, they are inactivated by cellular defense mechanisms that wrap the viral genome in repressive chromatin structures. In order for viral replication to progress, the host’s own histone demethylases are recruited to the viral genome to reverse this repression.

Novel Therapeutic Compounds for Treatment of Cancer and Immune Disorders

The global market for cancer therapeutics is over $40 billion and is anticipated to continue to rise in the future. There remains a significant unmet need for therapeutics for cancers that affect blood, bone marrow, and lymph nodes and the immune system, such as leukemia, multiple myeloma, and lymphoma. The proteasome inhibitor bortezomib, which may prevent degradation of pro-apoptotic factors permitting activation of programmed cell death in neoplastic cells dependent upon suppression of pro-apoptotic pathways, has been a successful mode of treatment for such cancers.

Compounds That Treat Malaria and Prevent Malaria Transmission

Malaria is the single leading cause of death, especially among children, in the developing world. Malaria is caused by infection with parasites of the genus Plasmodium, transmitted by mosquitos. In addition to transmission, vital steps in the parasite lifecycle occur in the mosquito host. The invention offered for licensing relates to therapeutic compounds and related pharmaceutical compositions that can be used in the prevention and treatment of malaria infection.

Improved Standard for Immune System Recovery Assay

Monitoring an immune system that has been depleted by infection (e.g., HIV), chemotherapy, or progenitor cell transplantation is vital to assessing individual’s recovery status. This technology provides a new plasmid standard to be used as part of the existing TREC assay. This new plasmid has a shorter insert than the commercially available one, which means it now matches the PCR product generated in the qPCR reaction in the TREC assay. Additionally, the new plasmid is easier to grow up than the existing standard.

Multivalent Vaccines for Rabies Virus and Filoviruses

No vaccine candidates against Ebola virus (EBOV) or Marburg virus (MARV) are nearing licensure and the need to develop a safe and efficacious vaccine against filoviruses continues. Whereas several preclinical vaccine candidates against EBOV or MARV exist, their further development is a major challenge based on safety concerns, pre-existing vector immunity, and issues such as manufacturing, dosage, and marketability. The inventors have developed a new platform based on live or chemically inactivated (killed) rabies virus (RABV) virions containing EBOV glycoprotein (GP) in their envelope.

Monoclonal Antibodies Against Poliovirus

Early work by Hammond at al. showed gamma globulin to be effective for the prevention of poliomyelitis. Therefore, passive immunotherapy could be another way to treat chronic excretors. Even though prior attempts to use intravenous immunoglobulin (IVIG) and breast milk were unsuccessful, there is reason to think that higher doses of antipoliovirus antibodies could result in complete clearance of poliovirus from chronically infected individuals.

Methods of Treating Giardiasis Using FDA-Approved Compounds

This technology includes a group of at least twenty-nine, diverse, commercially available compounds that are newly identified for activity against Giardia lamblia parasites. At least six of the candidate compounds, Bortezomib, Decitabine, Hydroxocobalamin, Amlexanox, Idarubicin, and Auranofin have preexisting FDA approval for human use for other (non-Giardia) conditions. Another three compounds, Fumagillin, Nitarsone and Carbadox have preexisting approval for veterinary use for non-Giardia conditions.

Transgenic Mice Expressing Human Arginase II Gene in Endothelium: Useful for Studying Atherosclerosis and Other Vasculopathies

Cardiovascular disorders associated with endothelial dysfunction, like atherosclerosis, have decreased endothelial nitric oxide (NO) bioavailability. L-arginine, the primary substrate for endothelial nitric oxide synthase (eNOS), is important in the regulation of NO production. Arginase competes with eNOS for L-arginine and has been implicated in the endothelial dysfunction. NIH investigators have generated transgenic mice with human ArgII (hArgII) gene under control of endothelial-specific Tie2 promoter. In these mice, hArgII was expressed at very high levels in all tissues except liver.