Described herein are block copolymers, and methods of making and utilizing such copolymers. The described block copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the block copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the block copolymer is endosomolytic and capable of delivering an oligonucleotide (e.g., an mRNA) to a cell. Compositions comprising a block copolymer and an oligonucleotide (e.g., an mRNA) are also disclosed.

The purpose of the present invention is to provide a set of two polypeptides for use in light-dependent genetic recombination in which the N-terminal side fragment and the C-terminal side fragment of a Cre protein having an amino acid sequence of SEQ ID NO: 1 respectively bind to two proteins light-dependently forming a dimer.

The present invention relates, in part, to methods of treating a cancer in a subject comprising administering to the subject a therapeutically effective amount of an agent that inhibits one or more biomarkers listed in Table 1, such as regulators of ubiquitin proteasome pathway (e.g., STIP1 homology and U-Box containing protein 1 (STUB 1), ubiquilin-1 (UBQLN1), and heat shock protein 90 kDa beta member 1 (HSP90B 1)), in combination with an immunotherapy.

The present invention provides a composition which comprises the following Thyroid Stimulating Hormone Receptor (TSHR) peptides: (i) all or part of the amino acid sequence KKKKYVSIDVTLQQLESHKKK (SEQ ID NO: 1), or a part thereof, or a sequence having at least 60% sequence identity to SEQ ID NO:1; and (ii) all or part of the amino acid sequence GLKMFPDLTKVYSTD (SEQ ID NO: 2), or a part thereof, or a sequence having at least 60% sequence identity to SEQ ID NO:2. The present invention also relates to the use of such a composition for the prevention or suppression of activating autoantibody formation in Graves' disease.

Described herein are block copolymers, and methods of making and utilizing such copolymers. The described block copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the block copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the block copolymer is endosomolytic and capable of delivering an oligonucleotide (e.g., an mRNA) to a cell. Compositions comprising a block copolymer and an oligonucleotide (e.g., an mRNA) are also disclosed.

Nonsense-mediated mRNA decay (NMD) polypeptides, nucleic acids encoding NMD polypeptides, and methods of using such polypeptides and nucleic acids in the treatment of ALS and in screening for agents for the treatment of ALS are described.

The present invention relates to a method for reducing the competitive fitness of an organism hemizygous for a transgenic locus compared to the organism homozygous for the transgenic locus comprising the steps of: (a) reducing the expression of a haploinsufficient gene in the organism, wherein said reduction is conveyed by a transgenic locus in the organism; and (b) rescuing the reduced expression in the organism, wherein said rescue is conveyed by the same transgenic locus in the organism, yielding an organism which is less competitively fit if hemizygous for the transgenic locus than if homozygous for the transgenic locus. The present invention also relates to a method for decreasing the introgression of a transgenic locus in an organism into a population of otherwise interfertile sexually reproducing organisms comprising the steps of: (a) reducing the expression of a haploinsufficient gene in the organism, wherein said reduction is conveyed by a transgenic locus in the organism; (b) rescuing the reduced expression in the organism, wherein said rescue is conveyed by the same transgenic locus in the organism, and (c) using a transgenic organism obtained in step (b) in an environment comprising otherwise interfertile sexually reproducing wildtype individuals of the organism, wherein the competitive fitness of hemizygous progeny is reduced, thereby decreasing the rate of sexually reproduction and/or viability and/or the competitive fitness of hemizygous progeny. Further envisaged are corresponding genetic systems and genetically modified organisms.

Provided is an improved design of shRNA based on structural mimics of miR-451 precursors. These miR-451 shRNA mimics are channeled through a novel small RNA biogenesis pathway, require AGO2 catalysis and are processed by Drosha but are independent of DICER processing. This miRNA pathway feeds active elements only into Ago2 because of its unique catalytic activity. These data demonstrate that this newly identified small RNA biogenesis pathway can be exploited in vivo to produce active molecules.

Based on the discovery that MBLAC1 is a specific, high-affinity target for Ceftriaxone (Cef), MBLAC1 may be used for identifying molecules and molecular networks associated with MBLAC1's role in the actions of substances of abuse, e.g., molecules and networks of molecules modulated by Cef in an animal that expresses MBLAC1 and is administered a substance of abuse and not in an animal that does not express MBLAC although administered the same substance of abuse. Methods for identifying MBLAC1-dependent molecules and molecular networks include analyzing and comparing levels of molecules (nucleic acids, neurotransmitters, proteins, and metabolites) in MBLAC1 knock-out animals and wild-type MBLAC1 animals. These methods and MBLAC1 knock-out animals can also be used for identifying therapeutic drug targets for treatment of addiction to, or withdrawal from, a substance of abuse.

As disclosed herein, the invention relates to a method of screening for a therapeutic for chronic myeloid leukemia. In an aspect, the invention relates to transgenic Drosophila. In an aspect, the invention relates to a Drosophila system for screening compounds treating chronic myeloid leukemia.