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Congenital disorders of glycosylation (CDGs) are a group of inborn errors characterized by abnormalities in the process of glycosylation of biomolecules. Although more than 100 different CDGs have been reported, only one has been thoroughly described, namely NGLY1 deficiency or NGLY1-CDG. NGLY1 encodes N-glycanase 1, an enzyme involved in the cytosolic degradation of misfolded glycoproteins and other glycoproteins bound for degradation.

Congenital disorders of glycosylation (CDGs) are inherited disorders of abnormal protein glycosylation that affect multiple organ systems. More than 100 different CDGs have been described, affecting protein and lipid glycosylation. NHGRI investigators have been able to isolate fibroblasts from patients with PMM2 (phosphomannomutase)-CDG, also known at CDG type Ia, which is an inherited, broad-spectrum disorder with developmental and neurological abnormalities.

This technology includes human cell lines from patients who have genetic defects in MOGS, the gene encoding mannosyl-oligosaccharide glucosidase, causing the rare congenital disorder of glycosylation type IIb, also known as MOGS-CDG. This defects appears to impair the ability of viruses to infect a second round of cells, which can be used to study and prevent infections. This is likely related to impaired viral replication and cellular entry. This finding has implications for Ebola and Zika, as well as other viral infections.

This technology includes a transgenic mouse model of Niemann-Pick Disease Type C (NPC), which is a rare neurodegenerative disorder, characterized by intracellular accumulation of cholesterol and gangliosides. The mouse strain, Tg(Npcl), expresses wild-type NPC1 gene under the control of the prion promoter. When combined with the NPC deficient mouse model, BALB/c npcnih/nih, also known as Npcl-/-, the transgene insertion allele rescues life expectancy of Npc1-/- mice. Npc1-/- mouse have reduced life expectancy and die around 8 weeks, making it a difficult model to be utilized.

This technology includes transgenic mice to be used in the study of melanocyte stem cells (MSCs) for utilization in regenerative medicine. Using the melanocyte system as a model, we investigated establishment of MSCs in the hair bulge - the stem cell compartment of the hair. During embryogenesis, all melanoblasts express SOX10, but this expression is downregulated during hair follicle morphogenesis and MSC differentiation. To further study the role of SOX10, we generated transgenic mice overexpressing SOX10 in melanoblasts.

This technology includes an alternative source of plasmid DNA produced in eukaryotic cells for non-viral gene transfer, which represent a novel eukaryotic alternative to bacterial plasmid DNA. Once introduced into non-dividing cells, ceDNA persists and transgene expression remains stable whereas plasmid (p) DNA is lost. The ceDNA and transfection reagent complex is nonimmunogenic allowing re-administration as needed: recombinant adeno-associated virus (rMV) is immunogenic precluding repeated administration.

This technology describes a series of small-molecule activators of the pyruvate kinase M2 isoform (PK-M2).

This technology includes small molecule inhibitors of the cdc2-like kinase (Clk) and Dyrk kinase which can restore splicing outcomes within many dysregulated splicing events potentially reversing phenotypes associated with diseases associated with abnormal splicing. The Clks regulate the alternative splicing of microtubule-associated protein tau and are implicated in frontotemporal dementia and Parkinson's disease through the phosphorylation of splicing factors (SF).

This technology is a collection of small molecule activators of a genetically defective version of the enzyme called glucocerebrosidase (GCase), which causes Gaucher disease. Gaucher disease is a rare disease affecting 1 in 40,000 babies born. Ashkenazi Jews of eastern European descent (about 1 in 800 live births) are at particular risk of carrying this genetic defect. It is caused by inherited genetic mutations in the gene that encodes GCase, which result in reduced activity of the enzyme.

NIH investigators have discovered a series of small compounds with the potential to treat a variety of cancers as well as hemolytic anemia. Contrary to most cancer medications, these molecules can be non-toxic to normal cells because they target a protein specific to the metabolic pathways in tumors, thus representing a significant clinical advantage over less-specific chemotherapeutics.