Presented are methods of assessing the teratogenicity of agents by measuring the degradation of SALL4, and related compounds with reduced teratogenicity. Provided herein is a method for assessing the teratogenicity of an agent comprising: contacting an agent with SALL4; and measuring levels of SALL4, wherein the agent is teratogenic if SALL4 levels are substantially reduced in the presence of the agent relative to in the absence of the agent.

The present invention relates to cell-penetrating effector proteins of type III secretion system (T3SS)-containing bacteria of the genus Salmonella or Shigella and variants, fragments and immunomodulatory domains thereof, for use in immunotherapy. The present invention further relates to cell-penetrating effector proteins of type III secretion system (T3SS)-containing bacteria of the genus Salmonella or Shigella and variants, fragments and immunomodulatory domains thereof, for delivering cargo molecules into eukaryotic cells.

Certain embodiments are directed to methods and compounds for inhibiting UBE3A-ATS, the endogenous antisense transcript of ubiquitin protein ligase E3A (UBE3A). Such methods and compounds are useful for. Several embodiments provided herein relate to the discovery that antisense compounds targeting UBE3A-ATS induce paternal expression of UBE3A. Several embodiments are drawn to methods and compounds for inducing paternal expression of UBE3A using antisense compounds targeting UBE3A-ATS within a region of UBE3A-ATS that includes the sequence of the small nucleolar RNA (snoRNA), HBII-85 (also referred to as SNORD116).

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

The present invention relates to an isolated chimeric molecule comprising a degradation domain including a eukaryotic U-box motif and a targeting domain capable of immunospecifically directing the degradation domain to a substrate where the targeting domain is heterologous to the degradation domain. A linker couples the degradation domain to the targeting domain. Also disclosed are compositions as well as methods of treating a disease, substrate silencing, screening agents for therapeutic efficacy against a disease, and methods of screening for disease biomarkers.

The present disclosure provides compositions and methods for treating subjects at risk for or with sensorineural hearing loss by modulating the rate of Atoh1 protein degradation to increase levels of Atoh1 protein.

The present disclosure relates to compounds for activating the enzymatic activity of an E3 ubiquitin ligase and methods for treating a disease or disorder in a subject with diminished E3 ubiquitin ligase enzymatic activity. In some embodiments, the present disclosure provides a compound of Formula (I) or a compound of Formula (II) or pharmaceutically acceptable salts thereof.

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A novel vector, composition and method of treating a UBE3A deficiency disease is presented. A novel UBE3A vector construct was generated with an additional secretion sequence to allow the secretion from cells. This secreted only E6AP protein maintains its presence outside the cell and is capable of diffusing to greater distances to cover more of the brain and rescue disease pathology.

The present disclosure provides an isolated invasive cancer stem cell (iCSC) or a substantially homogeneous iCSC population comprising said iCSC, which is positive for the marker AMFR on the cell membrane. The present disclosure also provides a method of detecting the iCSC within an established cancer or a collection of cancer cells. The present disclosure also provides a method of isolating the iCSC or a substantially homogeneous cell population comprising said iCSC from an established cancer or a collection of cancer cells.

The present invention relates to compounds which bind to Beta Trans-ducin repeat-containing protein (TrCP), and modulate the activity of TrCP. In particular, the invention relates to compounds which demonstrate optimised binding to PTrCP. The invention also relates to pharmaceutical compositions comprising such compounds and the use of such compounds as medicaments, specifically for the treatment of disorders associated with aberrant protein degradation, such as cancer. The preferred binding inhibitors are peptides derived from the motive DSGXXS, e.g. DEGFWE, DDGFWD and Succinyl-EGFWE.