Compositions for CDKL5 gene therapy are provided, as well as recombinant CDKL5 proteins. Such CDKL5 gene therapy compositions and/or recombinant CDKL5 proteins may incorporate cell-penetrating polypeptides and/or leader signal polypeptides. Also provided are methods of producing such gene therapy compositions and recombinant CDKL5 proteins, as well as pharmaceutical compositions, methods of treatment, and uses of the gene therapy compositions and recombinant CDKL5 proteins.

The present invention relates to a method of increasing resistance against fungal pathogens of the order Pucciniales, preferably the family Phacopsoraceae, in plants and/or plant cells. This is achieved by increasing the expression of an RLK1protein or fragment thereof in a plant, plant part and/or plant cell in comparison to wild type plants, wild type plant parts and/or wild type plant cells. Furthermore, the invention relates to transgenic plants, plant parts, and/or plant cells having an increased resistance against fungal pathogens, in particular, pathogens of the order Pucciniales, preferably the family Phacopsoraceae, and to recombinant expression vectors comprising a sequence that is identical or homologous to a sequence encoding an RLK1protein.

This invention relates to compositions and methods for modifying root architecture in a plant through modification of an endogenous Ser-Thr protein kinase gene, such as endogenous PHOSPHOROUS STARVATION TOLERANCE 1 (PSTOL1) nucleic acids. The invention further relates to plants produced using the methods and compositions of the invention.

The present invention provides, in order to prepare matured hepatocytes analogous in various points to primary hepatocytes, a method for preparing hepatocytes or cells that can be differentiated into hepatocytes from pluripotent stem cells, comprising the steps of: (1) culturing the pluripotent stem cells in a medium containing an activator of an activin receptor-like kinase-4,7; (2) culturing the cells obtained in the step (1) in a medium containing a bone morphogenetic factor and a fibroblast growth factor; (3) culturing the cells obtained in the step (2) in a medium containing an activator of a hepatocyte growth factor receptor and an activator of an oncostatin M receptor; and (4) culturing the cells obtained in the step (3) to obtain hepatocytes or cells that can be differentiated into hepatocytes, wherein in at least one of the steps (2), (3) and (4), cells are cultured on a high-density collagen gel membrane.

Provided are methods and compositions for promoting tissue (e.g., muscle) regeneration using one or more activators of fatty acid oxidation, such as one or more PPARγ activators. The methods and compositions described herein are also useful for promoting tissue growth, inducing proliferation of stem cells, inducing differentiation of tissuegenic cells (e.g., myogenic cells), and treating a disease or condition associated with a tissue (e.g., muscle), such as tissue injury, degeneration or aging, in an individual.

The invention is directed to methods of treating TNBC in a patient by administering to the patient an agent that inhibits the expression or activity of cyclin-dependent kinase 19 (CDK19). In some embodiments, the agent may be a small molecule inhibitor, a polynucleotide (e.g., shRNA. siRNA), or a protein (e.g., an antibody). In some embodiments, the agent does not inhibit the activity or expression of CDK8.

Disclosed are compositions and methods for mediating immunosuppressive myelopoiesis. Additionally, disclosed herein are combination therapies for treating cancers and methods of using the same.

Provided herein are methods, compounds, and compositions for reducing expression of a DMPK mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for preferentially reducing CUGexp DMPK RNA, reducing myotonia or reducing spliceopathy in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate type 1 myotonic dystrophy, or a symptom thereof.

Certain embodiments of the invention provide a method of detecting the presence of a biomarker associated with resistance to an mTOR kinase inhibitor in a subject, comprising determining the presence of the biomarker in a physiological sample from the subject, wherein the sample comprises a nucleic acid.

Provided herein are methods, compounds, and compositions for reducing expression of a DMPK mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for preferentially reducing CUGexp DMPK RNA, reducing myotonia or reducing spliceopathy in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate type 1 myotonic dystrophy, or a symptom thereof.