Simple, Rapid, and Sensitive Real-Time PCR Assays for Detecting Drug Resistance of HIV

This novel assay features real-time PCR reagents and methods for detecting drug-resistance related mutations in HIV, for newly diagnosed patients and those individuals currently receiving antiretroviral therapies. As the use of antiretroviral compounds to treat HIV infection proliferates, viruses adapt and evolve mutations limiting the efficacy of these drugs and disrupting the success of treatment.

Multiplexing Homocysteine in Primary Newborn Screening Assays Using Maleimides as Select Derivatization Agents

Homocystinuria (HCU), a group of inherited disorders, causes symptoms ranging from failure to thrive and developmental delays in infants or young children to abnormal blood clots with onset in adults.1 Approximately 1 in 200,000 to 335,000 people have HCU globally.2

4G10, a Monoclonal Antibody Against the Chemokine Receptor CXCR4, Raised Against a Synthetic Peptide of 38 Residues in Length Derived from the N-terminal Sequence of CXCR4

This invention identifies a monoclonal antibody (4G10) against the chemokine receptor CXCR4 and is a mouse IgG1 antibody. CXCR4 has been identified as a co-receptor mediating entry of HIV-1 into T cells. Subsequently, CXCR4 has been implicated in normal physiological functions, including activation of B cells and B cell progenitors and guiding their migration into the bone marrow (via its ligand SDF-1). CXCR4 also functions in T cell progenitor migration and neural progenitor stem cell activation.

Method of Producing Immortalized Primary Human Keratinocytes for HPV Investigation, Testing of Therapeutics, and Skin Graft Generation

One of the major limitations of using cultured keratinocytes for research studies is that primary keratinocytes senesce after a few passages. Keratinocytes from specific anatomical sites are also difficult to culture. Scientists at the NIH have demonstrated that primary keratinocytes, from several anatomical sites, when treated with a small-molecule inhibitor of the ROCK protein maintain a proliferative state and become immortal without genetic modification to the cells.

HLA-class II-restricted T Cell Receptors for PIK3CA “Hotspot” Mutations, E545K and N345K

Summary: 

The National Cancer Institute (NCI) seeks co-development partners and/or licensees for a collection of T cell receptors (TCRs) that specifically target PIK3CA mutations to treat patients with tumors expressing these mutations in the context of HLA-DPA1*01:03:01, HLA-DPB1*04:01:01 or HLA-DRB1*04:01.

Description of Technology:

Next-Generation 5-HT-2B Serotonin-Receptor Antagonists for Anti-Fibrotic & Cardiopulmonary Therapy

This technology includes a family of small-molecule antagonists that selectively block the 5-HT2B serotonin receptor—an upstream driver of tissue-remodeling—to address fibrotic, cardiopulmonary and related disorders. Built on a conformationally-locked “(N)-methanocarba” nucleoside scaffold, the compounds show nanomolar potency, >30–400-fold selectivity over the closely related 5-HT2C receptor, and favorable oral bioavailability in rodents.

Bicistronic Chimeric Antigen Receptor (CAR) Constructs Targeting CD19 and CD20

CD19 and CD20 are promising targets for the treatment of B-Cell malignancies.  Unfortunately, some clinical studies have shown that there is a loss of CD19 or CD20 expression in various cases of lymphomas and leukemias, particularly after treatment with an agent that targets CD19 (e.g., anti-CD19 CAR-T). However, studies have shown that expression of one protein is retained when the other is lost. This suggests that a therapeutic with the ability to simultaneously target both CD19 and CD20 could represent a solution to the drawbacks of current therapies. 

Anti-SLAMF7 Chimeric Antigen Receptors

Immortalization of plasma cells leads to Multiple Myeloma (MM). Signaling Lymphocyte Activation Molecule F7 (SLAMF7) is highly expressed on the malignant plasma cells that constitute Multiple Myeloma. The expression of SLAMF7 by MM cells and lack of expression on nonhematologic cells makes SLAMF7 a promising target for chimeric antigen receptor (CAR) T cell therapies for the treatment of MM. 

Optimized Monospecific or Bicistronic Chimeric Antigen Receptor (CAR) Constructs Targeting CD19 and CD20

Patients with chemotherapy-refractory, diffuse large B-cell lymphoma (DLBCL) have poor prognoses. CD19 and CD20 are promising targets for the treatment of B-Cell malignancies. However, despite the initial promising results from anti-CD19 CAR therapy, only 30-35% of patients with DLBCL achieve remissions lasting longer than 2-3 years after anti-CD19 CAR T-cell therapy. Relapse and non-response are likely due to diminished CD19 expression after anti-CD19 therapy and low expression of CD19 in some lymphomas. 

Optical Trap Methods to Determine the Viscoelastic Properties of Biological Materials

Optical traps (optical tweezers) have a focused laser beam able to trap a small bead at its focus, and are used to measure the microrheology of gels and other materials. They have recently been used to characterize properties of living cells, however issues of image spatial resolution and limited depth of interrogation have prevented application of an optical trap to measure microrheological (flow of matter) properties in complex (non-uniform) materials, such as multi-cellular systems or living organisms. 

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