Viral Entry or Replication Inhibitors

The Tec family of tyrosine kinases, consisting of five family members Tec, Btk, Itk, Rlk, and BMX, are key regulators of signaling pathways of T lymphocytes. Many existing antiviral therapies rely on inhibition of viral replication, which leads to emergence or selection of resistant viruses. The current technology provides an alternative method for prevention or treatment of viral infection through administration of a Tec tyrosine kinase inhibitor. Such inhibitors can be siRNA, small chemical compounds, antisense or antibody.

Genes For Niemann-Pick Type C Disease

Niemann-Pick disease is a class of inherited lipid storage diseases. Niemann-Pick Type C disease is an autosomal recessive neurovisceral lipid storage disorder which leads to systemic and neurological abnormalities including ataxia, seizures, and loss of speech. Patients with the disease typically die as children. The biochemical hallmark of Niemann-Pick Type C cells is the abnormal accumulation of unesterified cholesterol in lysosomes, which results in the delayed homeostatic regulation of both uptake and esterification of low density lipoprotein (LDL) cholesterol.

Specific Inhibition of Gene Expression by Small Double Stranded RNAs

Double-stranded RNA (dsRNA) has been shown to trigger sequence-specific gene silencing in a wide variety of organisms, including plant, nematode and invertebrate species. Recent intense work in the field has shown that small dsRNAs mediate sequence specific RNA degradation in the process known as RNA interference (RNAi).

This invention provides for synthetic dsRNAs (20-25 nucleotides in length) and methods that can inhibit gene-specific expression in mammalian cells.

A Mouse Model of Multiple Endocrine Neoplasia, Type I

The current invention embodies a mouse model which is heterozygous for a null allele at the Men1 locus of murine chromosome 19. Men1 has similar exon-intron organization and amino acid identity compared with its human analog MEN1, which has been implicated in the pathogenesis of multiple endocrine neoplasia, type I (MENI). This mouse model has been shown to develop features remarkably similar to those of MEN1, which include tumors of the endocrine pancreas, pituitary, and parathyroids.

Clonal Spodoptera Frugiperda Cell lines for Enhanced Expression

This technology includes Spodoptera frugiperda (Sf9) cells which were developed to produce recombinant adeno-associated virus. The cells maintain a copy of the vector genome and for production, require infection with a single baculovirus that expresses either structural and nonstructural proteins to produce rAAV, or the non-structural (Rep) proteins to produce ceDNA.

Mouse Models of Cryopyrin-Associated Periodic Syndrome (CAPS) for Drug Discovery

This technology includes mouse models that express versions of mouse cryopyrin protein containing mutations associated with human CAPS disease. We engineered mutations associated with three specific CAPS phenotypes (familial cold autoinflammatory syndrome (FCAS); Muckle-Wells syndrome (MWS); and neonatal onset multisystem inflammatory disease (NOMID)) into the mouse cryopyrin gene (called Nlrp3) to examine the roles of IL-1 β and related cytokines, and better characterize inflammasome functions.

Selections of Genes

The invention provides selections of genes expressed in a cancer cell that function to characterize such cancer, and methods of using the same for diagnosis and for targeting the therapy of selected cancers. In particular, methods are provided to classify cancers belonging to distinct diagnostic categories, which often present diagnostic dilemmas in clinical practice, such as the small round blue cell tumors (SRBCTs) of childhood, including neuroblastoma (NB), rhabdomyosarcoma RMS), Burkitt’s lymphoma (BL), and the Ewing family of tumors (EWS).

Farnesyltransferase Inhibitors for Treatment of Laminopathies, Cellular Aging and Atherosclerosis

Hutchinson-Gilford Progeria Syndrome (HGPS) is a very rare progressive childhood disorder characterized by premature aging (progeria). Recently, the gene responsible for HGPS was identified (Eriksson M, et al. Nature 2003), and HGPS joined a group of syndromes — the laminopathies — all of which are caused by various mutations in the lamin A/C gene (LMNA). Lamin A is one of the family of proteins that is modified post-translationally by the addition of a farnesyl group.

Monoclonal Antibody to the Protein NCOA6 (also called ASC-2, AIB-3)

The invention relates to monoclonal antibodies that bind to the transcription factor NCOA6 (ASC-2, AIB-3, TRB, TRAP250, NRC). The antibodies have proven successful reagents for Western blotting and for purifying complexes containing NCOA6. The Western blot experiments revealed that NCOA6 is over-expressed in several breast cancer cell lines, and the purification experiments identified a protein complex containing NCOA6 (the ASCOM complex). The monoclonal antibodies may be useful reagents for studying the role of NCOA6 in transcription and for studying the ASCOM complex.
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