Tau protein has a causative role in Alzheimer's disease and multiple other neurodegenerative disorders exhibiting tau histopathology collectively termed tauopathies. The primary function of tau protein is to facilitate assembly and maintenance of microtubules in neuronal axons. In the disease process tau protein becomes modified, loses its affinity to microtubules and accumulates in the cell body where it forms aggregates. The large neurofibrillary tangles formed from tau protein assembled into filaments were thought to be the pathological structure of tau. However, more recent work indicates that smaller, soluble oligomeric forms of tau are best associated with neuron loss and memory impairment. Here, novel compositions of tau oligomers and novel mechanisms for tau oligomer nucleation, extension and termination are taught. Methods for producing and purifying these structures for the development of small molecule and immunotherapeutics as well as antibodies for biomarkers of neurodegenerative diseases are taught.

The present disclosure concerns genetically modified host cells that express an immunoproteasome in the absence of induction by or contact with a cytokine. The genetically modified stem cells are useful, for example, for vaccine production, and identification of new target antigens.

The present disclosure provides, in part, compositions and methods for transient removal of neutralizing antibodies directed to AAV vectors. Such compositions and methods expand the patient cohort eligible for gene therapy and also for redosing/re-administration of AAV in patients previously treated with AAV vectors.

To provide a novel pharmaceutical use of a peptide. A pharmaceutical composition for the treatment or prevention of retinitis pigmentosa, comprising a peptide which comprises the amino acid sequence shown in SEQ ID NO: 30 and inhibits the protease activity.

Compositions and methods for improving embryo development, treating idiopathic male factor infertility, and enabling infertile/sub-fertile/sterile men to father their own genetic offspring are provided. Typically, the methods include administering into a male or female gamete or fertilized embryo an effective amount of a compound that increases bioavailability of a TET protein to improve development of an embryo resulting from fertilization of the female gamete by a male gamete. The compound can be administered into the gamete or embryo before, during, or after fertilization. The compound can be administered by an injection such as intracytoplasmic injection. The compound and the male gamete can be administered in combination by intracytoplasmic sperm injection. Methods of making male gametes, and methods of modifying the genome of a male gamete or embryo using an effective amount of a gene editing composition to correct a gene mutation or anomaly in the genome thereof are also provided.

This application relates to adeno-associated viral vectors encoding a truncated yet functional ATP7B for use in gene therapy for treating Wilson disease (WD). The truncated ATP7B described herein has several advantages over the wild-type ATP7B such as higher efficacy and improved manufacturing yield.

Tau protein has a causative role in Alzheimer's disease and multiple other neurodegenerative disorders exhibiting tau histopathology collectively termed tauopathies. The primary function of tau protein is to facilitate assembly and maintenance of microtubules in neuronal axons. In the disease process tau protein becomes modified, loses its affinity to microtubules and accumulates in the cell body where it forms aggregates. The large neurofibrillary tangles formed from tau protein assembled into filaments were thought to be the pathological structure of tau. However, more recent work indicates that smaller, soluble oligomeric forms of tau are best associated with neuron loss and memory impairment. Here, novel compositions of tau oligomers and novel mechanisms for tau oligomer nucleation, extension and termination are taught. Methods for producing and purifying these structures for the development of small molecule and immunotherapeutics as well as antibodies for biomarkers of neurodegenerative diseases are taught.

Mammalian cell lines genetically engineered to have reduced or eliminated expression of specific host cell proteins, and methods for using the engineered mammalian cell lines for the production of recombinant proteins having low levels of residual host cell protein contamination.

Embodiments provided here include recombinant polypeptides, termed degradons, comprising a target binding domain and a proteasome-binding domain. Degradons of the embodiments are able to selectively target and degrade proteins bound by the target-binding domain, such as proteins associated with disease. Vectors encoding degradons and methods of treating disease with degradons and degradon expression vectors are likewise provided.

Provided herein are methods and compositions for treatment of Batten disease. Such compositions include a recombinant adeno-associated virus (rAAV), said rAAV comprising an AAV capsid, and a vector genome packaged therein, said vector genome comprising (a) an AAV 5 inverted terminal repeat (ITR) sequence; (b) a promoter; (c) a CLN2 coding sequence encoding a human TPP1; (d) an AAV 3 ITR.