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This invention relates to a novel gammaretroviral vector packaging cell line and a method of producing gammaretroviral vectors suitable for gene therapy. The described vectors may contain the gibbon ape leukemia virus (GALV) envelope with a CD11D8 epitope tag enabling their purification on a monoclonal antibody conjugated column. These vectors have several advantages over existing systems, including a broader host range, higher infectivity, and lower potential for replication.

This technology relates to a mouse model that improves an existing method of disrupting the production of the BDNF protein in specific parts of the brain. A current avenue of research seeks to examine how gene expression may effect long-lasting changes in the nervous system. Previous work has resulted in a mouse line in which the production of BDNF was disrupted. However, these mice had an inadvertent genetic component left in: a neomycin cassette. This unintentional addition led to significant deleterious effects.

This invention relates to novel mouse and rat models that permit the temporal death of neuronal precursor cells at any time point. Other existing methods of decreasing neurogenesis are relatively non-specific (e.g., injecting glucocorticoids) or require expensive equipment (e.g., focal x-irradiation)
These mice and rats are being used to inhibit adult neurogenesis in order to study the normal function of adult neurogenesis and to model disease states thought to feature decreased neurogenesis, such as chronic stress, anxiety, and depression.

This invention relates to the stable and high-yield production of a high-potency toxin protein called DT390-EGF. This toxin was developed for the treatment of EGF-receptor-positive cancers, including bladder cancer. Initial methods for synthesizing DT390-EGF relied on the use of E. coli. However, the production in E. coli was difficult to prepare and had limited stability. Repeated efforts to standardize the process in E. coli gave poor yields, purity, and high variation.

This technology includes the generation and use of an antibody that can detect endogenous Neuroligin 4Y, NLGN4Y, a cell adhesion molecule on the X-chromosome. NLGN4Y is part of an X-Y pair with NLGN4X, which has been implicated with autism spectrum disorder (ASD) and intellectual disability. ASD has a sex bias etiology that is not well understood, affecting four times as many males as females. Previous work has revealed a potential pathogenic mechanism for male-bias based on mutations in NLGN4X and NLGN4Y. The use of the NLGN4Y antibody could be used to study potential mechanisms.

This technology relates to the therapeutic use of antibodies to decrease the potential neurodegenerative effect of the HERV-K retrovirus. Previous work has shown that patients with Amyotrophic Lateral Sclerosis (ALS) can have HERV-K activation. In animal models, activation of HERV-K can lead to neurodegenerative symptoms similar to those exhibited by ALS patients. This neurodegenerative effect is thought to be caused by the release of HERV-K envelope proteins into the extracellular space. Work with monoclonal antibodies in vitro has neutralized the toxicity of this protein.

This invention includes human induced pluripotent stem cell (iPSC) lines that harbor a single copy dCas9-BFP-KRAB at the CLYBL safe harbor locus (mediating CRISPR inhibition of human gene expression) and/or a single copy of dox-inducible NGN2 at the AAVS1 locus (enabling the differentiation of the iPSCs into neurons). The CRISPR-mediated inhibition of human gene expression is maintained into the differentiated neurons, permitting functional studies of targeted genes in neurons.

This technology relates to the creation and use of newly identified ligands to the D1 dopamine receptor (D1R). The D1 dopamine receptor is linked to a variety of neuropsychiatric disorders and represents an attractive drug target for the enhancement of cognition in schizophrenia, Alzheimer disease, and other disorders. These ligands are positive allosteric modulators (PAMs) that bind to the dopamine receptor at a site other than where dopamine binds and causes the receptor to have an increased response.

The technology relates to therapeutic approaches that inhibit and block the replication of the endogenous HERV-K retrovirus. Previous work has shown that patients with Amyotrophic Lateral Sclerosis (ALS) can have HERV-K activation. In animal models, activation of HERV-K can lead to neurodegenerative symptoms similar to those exhibited by ALS patients. Work in these animal models has allowed the identification of the responsible transcription factor (TDP-43) as well as the corresponding positions of the HERV-K promoter binding sites.

The technology includes USP30 knockout HeLa cells that were generated using CRISPR technology. Parkin and Pink1 are key master genes for triggering the degradation of mitochondria (mitophagy). In contrast, USP30 has been found to be localized in the mitochondria and have a role in antagonizing Parkin function, thereby impeding mitophagy.