Immunogens, Compositions, and Methods for the Treatment of Dyslipidemia

This technology includes a novel vaccine for forming autoantibodies against apoC-III, a plasma enzyme that inhibits lipolysis. The vaccine can possibly be used to treat patients with high triglycerides and are at risk for pancreatitis and cardiovascular disease. This disclosure describes an ApoC3 immunogen that includes an antigenicApoC3 peptide linked to a bacteriophage virus-like-particle (VLP) immunogenic carrier.

Antibody Targeting of Cell Surface Deposited Complement Protein C3d as a Treatment for Cancer

This technology includes monoclonal antibodies (mAb) that specifically and with high affinity bind the final complement components C3dg and C3d (subsequently referred to as C3d), which can be used to kill tumor cells that carry C3d on their cell surface. We show that tumor cells of patients treated with the therapeutic anti-CD20 mAb ofatumumab carry C3d on the cell surface and can bind and be killed by addition of anti-C3 mAbs. In contrast, further addition of more ofatumumab has only minimal effects.

Transgenic Mouse Expressing Cre for the Development for Delivery of Gene Therapy

This technology includes a mouse model containing a hypothetical, previously undescribed, gene that we have proven is expressed in hair cells of the inner ear and few other tissues in the body. The hair-cell limited expression of Cre is a genetic tool for creating conditional mutations affecting hair cells almost exclusively. Hair cells are the sensory receptors of both the auditory system and the vestibular system in the ears of all vertebrates.

A BL21 (ED3) Codon Plus Competent Cell-derived Bacterial Strain for Research Use

This technology includes a bacterial strain derived from BL21 (ED3) CodonPlus Competent Cells containing an expression vector for human POLR2C gene for research purposes. The bacterial strain can be used to produce the full-length human RNA polymerase II subunit, RPB3 protein, which can be in turn isolated and purified.

Developing a Stable Cell as a Screening Tool for Environmental Chemicals

This technology includes a stable cell line (293T2-PGC) which has an intact PGC-1 alpha/ERR-alpha pathway to screen for environmental chemicals. The estrogen-related receptor alpha (ERR-alpha) and proliferator-activated receptor gamma coactivator - 1alpha (PGC-1 alpha) play critical roles in the control of several physiological functions, including the regulation of genes involved in energy homeostasis. However, little is known about the environmental chemicals that could disrupt or modulate this pathway leading to adverse health effects.

Inhibition of Epoxide Hydrolase 1 in the Treatment of Cardiovascular Diseases

This technology includes EPHX1/EPHX2 null mice and showed that disruption of both EPHX1 and EPHX2 almost completely abolished hydrolysis of several EETs which can be used in the treatment of cardiovascular diseases. EPHX 1 is significantly involved in EET hydrolysis, and we believe the combined use of EPHX1 and EPHX2 inhibitors would provide a better alternative to currently available therapeutic options or the EPHX2-based therapies currently in trials for the treatment of cardiovascular diseases.

Genetic Manipulation of Natural Killer Cells to Express c-MPL Growth Factor Receptor as a Therapy for Cancer

This technology includes genetic manipulation of natural killer (NK) cells to express thrombopoietin receptor (c-MPL) growth factor receptor as strategy to augment NK cell proliferation and anti-tumor immunity. Many investigational adoptive immunotherapy regimens utilizing NK cells require the administration of IL-2 or IL-15 cytokines to support the survival and function of the cells in patients, however administration of these cytokines causes a number of serious dose-dependent toxicities.

Functions and Targets of Therapeutic MicroRNAs to Treat and Diagnose Cancer

This technology includes a method to identify potentially therapeutic microRNAs in cancer, particularly squamous cell carcinoma of the head and neck (HNSCC). This approach first utilizes a large and publicly available expression dataset, which is then validated by a smaller independent dataset to determine deregulated microRNAs expression. These results are then intersected with in vitro functional anti-proliferative screening data to select for microRNAs that play a functional tumor suppressive role and likely serve as therapeutic targets.

Modulating Autophagy as a Treatment for Lysosomal Storage Diseases

Researchers at NIAMS have developed a technology for treatment of lysosomal storage diseases by inhibition of autophagy. Pompe disease is an example of a genetic lysosomal storage disease caused by a reduction or absence of acid alpha-glucosidase (GAA). Patients with Pompe disease have a lysosomal buildup of glycogen in cardiac and skeletal muscle cells and severe cardiomyopathy and skeletal muscle myopathy. Treatment of Pompe disease by GAA enzyme replacement therapy is quite ineffective for the skeletal muscle myopathy.