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.

Peptide vaccines against cancer are described herein. In particular, epitope peptides derived from the UBE2T that CTLs are provided. Isolated antigen-presenting cells with CTL inducibility and CTLs that target such peptides, as well as methods for inducing the antigen-presenting cell, or CTL are also provided. The present invention further provides pharmaceutical compositions containing such epitope peptides derived from UBE2T or polynucleotides encoding the polypeptides as active ingredients. Furthermore, the present invention provides methods for the treatment and/or prophylaxis of (i.e., preventing) cancers (tumors), and/or the prevention of a postoperative recurrence thereof, as well as methods for inducing CTLs, methods for inducing anti-tumor immunity, using the epitope peptides derived from UBE2T, polynucleotides encoding the peptides, or antigen-presenting cells presenting the peptides, or the pharmaceutical compositions of the present invention.

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

Provided are a polypeptide specifically binding to TRB3 and application thereof in preparation of drugs for treating and/preventing pulmonary fibrosis. The amino acid sequence of the polypeptide is represented by SEQ ID NO:12 in a sequence list, or two or more amino acids in the amino acid sequence as represented by SEQ ID NO:12 in the sequence list are replaced with unnatural amino acids having side chains that can be linked to each other. The polypeptide and derivatives thereof can specifically bind to TRB3, thereby blocking the interaction between TRB3 and MDM2 proteins.

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

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

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.

A CRISPR/Cas system and method for editing or regulating transcription of a genome of a cell are provided, wherein the system includes a Cas endonuclease fused with one or more degron sequences and at least one activatable cognate single guide RNA harboring an inactivation sequence in a non-essential region of the cognate sgRNA, wherein said inactivation sequence comprises one or more endonuclease recognition sites of, e.g., a ribozyme.

The invention provides ubiquitin variants that specifically bind to SCF E3 ligases, and use of these variants to modulate the activity of SCF E3 ligases.

The invention provides ubiquitin variants that specifically bind to HECT E3 ligases, and methods of using these variants to modulate the activity of HECT E3 ligases.