Main Menu

This technology includes a high-yield, easy-to-culture mouse neuronal cell model with nearly complete glucocerebrosidase deficiency representative of Gaucher disease (GD) to study pathophysiology and evaluate new therapies. GD is an autosomal recessive lysosomal storage disorder caused by loss-of function mutations in the GBA1 gene, which codes for the lysosomal hydrolase glucocerebrosidase (GCase).

NCATS has developed a highly diverse synthetic library that will allow for the rapid identification of novel nanobodies that bind to a wide arrange of target antigens. The humanized framework used to construct the library will facilitate the transition of lead candidates into patient studies. Several highly potent SARS-CoV-2 nanobodies (antibodies) have been identified and are available for further development.

NCATS is actively seeking licensing for the 1) a synthetic library and 2) the potent neutralizing antibodies with activity against SARS-CoV-2.

This technology includes lymphoblastoid cell lines from individuals genotyped as carrying the minor (G) allele of ABCA7 SNP rs113809142 [ss491752998; SNV-chr19-1007244], to be used for small molecule screening and eventual therapeutic development. The ABCA7 gene is the ATP-binding cassette, sub-family A (ABC1), member 7. It encodes a protein that is a transporter and has been associated with such diseases as neonatal respiratory failure and Asperger's syndrome. It is also known to play a role in phagocytosis of apoptotic cells by macrophages and may mediate cholesterol efflux.

This technology includes a panel of 46 genomic loci of DNA methylation (represented by CpG dinucleotides on different chromosomes) with application in blood-based cancer screening. The markers robustly distinguish tumor from normal samples using 8 loci and classify 13 different tumor types. Using 39 loci, inventors were able to discriminate between individual tumor types or peripheral blood. In 4052 tumor samples from 13 tumor types, the true positive rate of classification was 91.4%.

Children with Hutchinson-Gilford progeria syndrome (HGPS) suffer from acceleration of certain aging symptoms, mainly cardiovascular disease that generally leads to death from myocardial infarction and/or stroke. The cause of HGPS has been discovered to be a de novo point mutation in lamin A (LNMA) gene. NHGRI Scientist have generated a transgenic mouse model of HGPS. This mouse carries a bacterial artificial chromosome (BAC) with a De novo mutation 1824 C to T (G608G) mutated form of human LNMA.

Recent studies have identified the G-protein-coupled receptor (GPCR) for insulin-like 3 peptide (INSL3), relaxin family peptide receptor 2 (RXFP2), as an attractive target for the treatment of bone diseases such as osteoporosis and rare bone diseases such as osteogenesis imperfecta. Currently, the most effective available treatment for osteoporosis is an expensive hormone therapy that requires daily injections. A stable, orally deliverable drug is a much more desirable alternative. Our RXFP2 agonists perform as well as the natural ligand INSL3 in cellular assays.

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 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.

These patent applications describe the cloning and characterization of the full-length genome of adeno-associated virus type 4 (AAV4). AAV4, like other members of the AAV family, may be useful as a vector for gene therapy.

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.