Generating Conditional and Reverse Conditional Loss-of-Function Alleles in Mouse Casq2

Summary:

 The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) is seeking potential licensees interested in further developing or utilizing these Casq2 mouse strains. As a research tool, patent protection is not being pursued for this technology. More information to access these strains can be found here: https://www.jax.org/strain/036291 and https://www.jax.org/strain/036290.

Enhancing Activity of Bispecific Antibodies in Combination with Ibrutinib for the Treatment of Cancer

This technology includes the combination of a kinase inhibitor (specifically ibrutinib) with a bispecific antibody (specifically a CD19/CD3 bispecific antibody) to be used to treat cancer. CD19/CD3 bispecific antibodies (bsAbs) can be used to recruit endogenous T cells against CD19+ tumor cells via the formation of cytolytic synapses. lbrutinib, a BTK inhibitor, has been shown to normalize T cell dysfunction characteristic of CLL.

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.

A Neural Stem Line from a Niemann Pick C (NPC) Type 1 Patient for Therapy Development

This technology includes a neural stem cell (NSC) line derived from a Niemann Pick C (NPC) patient, aimed at advancing research and drug development for NPC, an inherited neurodegenerative disorder characterized by the accumulation of cholesterol in neurons. The NSCs, which serve as a crucial intermediate cell type, can be differentiated into any neuronal or glial cell of the brain or spinal cord under appropriate culture conditions. These cells originate from fibroblasts reprogrammed into induced pluripotent stem cells.

Neural Stem Cells from an iPSC Line Ubiquitously Expressing Green Fluorescent Protein for Basic Science Research and Cell Line Tracking

This technology involves neural stem cells (NSCs) derived from pluripotent stem cells (PSCs) that can differentiate into neurons and glia. The key feature of this technology is the CY2 EEF1A1 GFP iPSC line, which includes a green fluorescent protein (GFP) expressed under the EEF1A1 promoter, leading to its ubiquitous expression in cells. This characteristic makes the NSCs and the neural cells differentiated from this line exhibit green fluorescence. Such cells, when transplanted into animal models like mice and rats, can be easily tracked due to their fluorescence.

Conditional Cell Immortalization Plasmid for Basic Science Research

This technology includes a novel plasmid design for cell immortalization. It uniquely combines the conditional activation of human telomerase and c-myc genes through cumate addition, a method distinct from traditional immortalization techniques which commonly use SV40 T-antigen, telomerase, or c-myc. This plasmid also includes a GFP reporter and a puromycin resistance gene, enhancing the efficiency of the immortalization process.

Neuronal Differentiation of Neural Stem Cells with StemPro Embryonic Stem Cell Serum Free Medium for Research and Therapeutic Development

This technology involves an innovative method for differentiating neural stem cells (NSCs) into neurons, primarily for use in basic science research and in developing therapies for brain and spinal cord disorders. Existing methods for generating neurons from NSCs typically result in high efficiency but low survival rates, especially when neurons are dissociated and regrown. This new method utilizes Life Technologies StemPro embryonic stem cell serum-free medium, which significantly enhances differentiation efficiency into neurons with minimal cell death.

Enhanced S10-3 Cell Line for Advanced Hepatitis E Virus Research and Therapeutic Development

The Huh-7 cell line underwent a detailed sub-cloning process to enhance its effectiveness for Hepatitis E Virus (HEV) infection studies. This involved diluting and culturing cells in 96-well plates until confluent monolayers formed, followed by selection and expansion of the most suitable cells. The sub-clone S10-3, derived from this process, was identified as the most efficient for transfection and infection by HEV.

Systemic CRISPR Therapy for the Treatment of Inherited Diseases

This technology includes novel systemic adeno-associated virus (AAV)-mediated CRISPR gene therapy technology. While some diseases (e.g., retinal diseases) can be treated through local gene transfer, many diseases such as Duchenne Muscular Dystrophy (DMD) require systemic therapy. The CRISPR technology has two components, the Cas9 endonuclease, and the gRNA. To explore systemic CRISPR therapy, we co-delivered the AAV.Cas9 and AAV.gRNA vector to mdx mice, a mouse DMD model. Direct delivery to muscle yielded efficient gene correction.

Device for Closure of Transvascular or Transcameral Access Ports

This technology includes part of transcatheter aortic valve replacement and to enable non-surgical thoracic aortic aneurysm endograft repair. The invention enables a completely new way to access the arterial circulation to allow introduction of large devices, such as transcatheter aortic valve replacement, percutaneous left ventricular assist devices, and thoracic aortic endografts. It also can be used in most labeled and off-label applications of Amplatzer (AGA Medical, St Jude) nitinol occluder devices to occlude intracardiac holes and to allow non-surgical direct access to the heart.