The present invention provides new compositions and methods useful for the treatment and potential cure of beta-globinopathies such as sickle cell disease and beta-thalassemia by inhibiting the expression and/or activity of RIOK3.

The present disclosure provides half duplex compounds comprising a first oligomeric compound and a second, shorter, oligomeric compound, wherein the first oligomeric compound is complementary to a target nucleic acid and the second oligomeric compound is complementary to the first oligomeric compound. In certain embodiments, the compounds disclosed herein are useful for modulating the expression of extra-hepatic target nucleic acids.

Acetate is a potent microbial inhibitor which can affect the performance of yeast in ethanolic fermentation. The present disclosure provides a recombinant microbial host cell having (i) a first genetic modification for increasing the activity of one or more proteins that function in a first metabolic pathway to convert acetate into an alcohol in the microbial host cell; (ii) a second genetic modification for increasing the activity of one or more proteins that function in a second metabolic pathway to import glycerol in the recombinant microbial host cell (iii) a third genetic modification for increasing the activity of one or more proteins that function in a third metabolic pathway to convert a C5 carbohydrate into ethanol in the microbial host cell. The recombinant microbial host cell comprises and natively expresses native proteins that function in a fourth native metabolic pathway to produce glycerol in the microbial host cell.

A protein-based peptide drug carrier derived from the tetramerization domain of the chimeric oncogenic protein Bcr/Abl of chronic myeloid leukemia. Peptides to be delivered are grafted to the N-terminal helical region of Bcr/Abl tetramer. To facilitate cellular uptake, an Arg-repeating hexapeptide is added to the C-terminal end of the Bcr/Abl protein. The protein-based delivery strategy provides a clinically viable solution to p53-inspired anticancer therapy and is applicable to the development of many other peptide therapeutics to target other intracellular protein-protein interactions responsible for disease initiation and progression.

Inhibitory peptides for modifying RAF kinase protein dimerization are described. The peptides display a binding affinity for the dimer interface of a B-Raf, allowing for modification of RAF kinase dimerization, and inhibition of tumor growth. An embodiment of the disclosure is a peptide generated by modifying SEQ ID NO: 1, which corresponds to amino acids 503-521 of B-Raf kinase, e.g., cyclization, N-terminal capping, C-terminal capping, substitution of one or more amino acid residues, etc. The peptides disclosed herein include a modification to SEQ ID NO: 1 that can improve or otherwise alter binding affinity of the peptide to the dimer interface.

Provided is a gRNA targeting HPK1 and a method for editing HPK1 gene. The method can knock out the T cell HPK1 gene, enhance the T cell killing activity, increase the Th1 cytokine level of peripheral blood mononuclear cells, and knock out of the T cell HPK1 gene can also down-regulate the expression of PD-1 and TIM3 on the T cell surface and can inhibit the T cell depletion.

The present disclosure provides improved compositions for adoptive T cell therapies targeting CD33 for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith. The present disclosure also relates to adoptive T cell therapies targeting CD33 and another target antigen for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

The present invention provides a method of protecting the heart from damage, by administering to a patient at risk of such damage, a pharmaceutically effective amount of a composition which inhibits the interaction of RSK3 and mAKAPβ, or the expression or activity of one or both of those molecules. This composition may be in the form of a peptide that specifically inhibits mAKAPβ binding to RSK3 or in the form of an siRNA construct which inhibits the expression of RSK3.

CAR cells and humanized antibodies targeting DCLK1 expressed on/in tumor cells or circulating cancer cells are described as a new method of cancer treatment. The antibodies and cells are safe and effective in patients and can be used to treat cancer expressing the DCLK1 proteins.

Provided are methods and compositions which are useful for separating, isolating, detecting, and quantifying compounds of interest which have been modified chemically, enzymatically or catalytically from other compounds which have not been so modified. The modifications may take the form of functional groups which are gained, lost or retained by the compounds of interest.