The disclosure concerns compositions and methods for treatment of encephalopathies, including encephalopathies caused by, or associated with, and STXBP1 haploinsufficiency or mutation. Compositions and methods provided herein encompass AAV particles that induce expression of STXBP1, including inducing the expression of STXBP1 in central and/or peripheral nervous system cells.

Methods and compositions are provided for activating transcription in a mammalian cell.

A polynucleotide comprising a nucleotide sequence encoding methyl-CpG binding-protein 2 (MeCP2) operably linked to a strong promoter and a 3′-UTR, wherein the 3′-UTR is less than or equal to about 1000 bp in length.

Bag3 is a multifunctional protein expressed predominantly in the heart, the skeletal muscle, the central nervous system and in many cancers. Although BAG3 was cloned only a decade ago, studies have shown that genetic variants, particularly those that result in haplo-insufficiency, can lead to severe left ventricular dysfunction; however, the full mechanisms responsible have remained obscure. To obviate the influence of heart failure itself on the biology of Bag3, ransgenic mice harboring a single allele knock-out were studied between 8 and 10 weeks of age before any obvious signs of heart failure were evident. The results were surprising and informative. First, it was found that despite a normal phenotype, young Bag3.sup.+/− had marked changes in the proteome that were characterized by changes in proteins associated with metabolism and apoptosis. Consistent with this finding, a decrease in the levels of critical proteins charged with maintaining the mitochondrial membrane potential was observed. It was also found that young mice shifted from a balance between the extrinsic and intrinsic pathways of apoptosis. However, in the presence of stress and the absence of Bag3 there was a shift from a balanced to an extrinsic dominant system (cleaved caspase 8). The diverse array of critical pathways regulated by Bag3 suggests a more important role especially during stress and that this role might include serving as an intracellular glue that holds proteins where they can be most effective rather than having them meet accidentally.

Provided are adeno-associated virus (AAV) compositions that can restore IDS gene function in cells, and methods for using the these AAV compositions to treat disorders associated with reduction of IDS gene function (e.g., Hunter syndrome). Also provided are compositions, systems and methods for making the AAV compositions.

The present disclosure provides a composition for preventing or treating a benign tumor. Provided is a composition for preventing or treating a benign tumor that comprises a WT1 peptide or an analog thereof, or a nucleic acid molecule encoding a WT1 peptide or an analog thereof. In a specific embodiment, the present disclosure provides a composition for preventing or treating a benign tumor that comprises a WT1 peptide or an analog thereof, or a nucleic acid molecule encoding a WT1 peptide or an analog thereof. In a preferred embodiment, the composition for preventing or treating a benign tumor (e.g. familial adenomatous polyposis) according to the present disclosure comprises a killer type WT1 peptide and/or a helper type WT1 peptide. In a further preferred embodiment, the WT1 peptide is WT1.sub.126 killer peptide and/or WT1.sub.35 helper peptide. In another aspect, provided are a method of inducing WT1 peptide-specific CTLs, a method of inducing WT1-specific helper T cells, and a method of inducing dendritic cells presenting a WT1 peptide.

This document provides methods and materials for treating aging. For example, a mammal having, or at risk for developing, an age-related impairment (e.g., age-related cognitive decline) can be treated by increasing the level of one or more myokine polypeptides (e.g., one or more Klotho polypeptides) within cells within the mammal. This document also provides methods and materials for increasing the ability of muscle progenitor cells to regenerate muscle cells by increasing the level(s) of one or more myokine polypeptides (e.g., an α-Klotho polypeptide) within a muscle progenitor cell.

Disclosed is a novel means which makes it possible to steadily mass-produce knockout individuals even in large animals. The method of the present invention is a method for producing a non-human large mammal or fish (non-human animal) that produces gametes originating in a different individual, and comprises transplanting at least one pluripotent cell derived from a second non-human animal into an embryo derived from a first non-human animal, said embryo being at a cleavage stage and having a genome in which a function of nanos3 gene is inhibited, to prepare a chimeric embryo, and allowing said chimeric embryo to develop into an individual.

Methods and compositions are provided for activating transcription in a mammalian cell.

Synthetic adenoviruses with liver detargeting mutations and expressing an adenovirus type 34 (Ad34) fiber protein, or a chimeric fiber protein with an Ad34 knob domain, are described. The synthetic adenoviruses traffic to sites of tumors. Use of the synthetic adenoviruses for delivering diagnostic or therapeutic transgenes to tumors are also described.