The present disclosure features useful compositions and methods to treat disorders for which deamination of an adenosine in an mRNA produces a therapeutic result,

K-Ras is the most frequently mutated oncogene in human cancer. Disclosed herein are compositions and methods for modulating K-Ras and treating cancer.

The present invention encompasses the recognition that identification of alternative means to block RAS oncogenic signaling may be required for developing novel cancer therapies. Among other things, the present invention encompasses the recognition that targeting RAS palmitoylation can achieve effective therapy for RAS-related cancers. Furthermore, the present invention encompasses the recognition that reduction of ZDHHC9 level and/or activity can significantly reduce palmitoylation level of Ras protein. Among other things, the present invention encompasses the recognition that identification of agents that modulate expression and/or activity of ZDHHC9 can reduce palmitoylation level of Ras protein. In some embodiments, the present invention provides methods of treating a subject suffering from cancer by administering ZDHHC9 inhibition therapy.

The present invention relates to peptide antagonists or inhibitors of GEF-H1, pharmaceutical compositions comprising said antagonists, polynucleotides encoding said antagonists, vectors encoding said polynucleotides, uses of said antagonists, pharmaceutical compositions and vectors in methods of medical treatment and kits comprising said antagonists, pharmaceutical compositions and vectors. The peptide antagonists of the present invention inhibit RhoA binding to the DH/PH module of GEF-H1 and, thereby, GEF-H1 function

Described herein is a method of modulating sumoylation of a Ras protein by small ubiquitin-like modifier (SUMO) proteins. Provided herein is a method for regulating the activity of a Ras protein. Also provided is a treatment of proliferative diseases, such as cancer, by introducing specific mutations to a mutant Ras protein that is associated with the proliferative disease. Described herein is a modified Ras protein. Described herein are recombinant vectors, cells comprising the vectors expressing the modified Ras proteins. Provided herein is an antibody that specifically binds to a sumoylated Ras protein. Described herein is a method for identifying an agent that interferes with the sumoylation of a Ras protein. Also described herein are therapeutic and prophylactic compositions. Also provided herein is a method of using a modified Ras protein to replace an endogenous mutant Ras protein that is associated with a proliferative disease.

The invention relates to generation and use of cellular and humoral responses for the prevention and treatment of P. gingivalis related conditions and diseases.

Mice comprising a transgene encoding a peptide (iBox) inhibitor of Group B p21-activated kinase are provided. Also provided are cells, tissue, and organs obtained from such transgenic mice. Also provided are methods for producing mice comprising an iBox-encoding transgene.

Disclosed herein are methods and kits useful for providing neuroprotection to neurons in the inner ear and to methods of treating inner ear diseases and disorders, including tinnitus and Mnire's disease.

This disclosure relates to the discovery that a G12V mutant of KRAS (hereinafter KRAS G12V) binds to JAK1, i.e., the existence of a KRAS G12V and JAK1 binding interaction. In certain embodiments, this disclosure relates to methods of disrupting the KRAS G12V and JAK1 interaction reversing KRAS G12V induced immune escape by cancer cells utilizing agents that prevent the binding of JAK1 to KRAS G12V.

The inventors have identified an autosomal dominant (AD) missense mutation in the RAC2 gene (coding for Ras-related botulinum toxin substrate 2 (RAC2)) in three Severe combined immunodeficiencies (SCID) patients whose clinical presentation overlaps with the RD SCID form but who lack AK2 mutations and deafness. Using biochemical and in vitro differentiation assays, the inventors demonstrated that the RAC2 mutation was closely related to an impairment in cell differentiation capacity and defects in cellular and mitochondrial networks. Taken as a whole, the data demonstrate that a dominant gain-of-function (GOF) mutation in the RAC2 protein's GDP/GTP binding site inhibits HSPC differentiation and leads to a severe AD form of SCID with a clinical presentation of RD. Accordingly, the results prompt to consider that introduction of the identified RAC2 mutein in the hematopoietic lineage would be suitable for inducing full ablation of hematopoiesis.

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