Disclosed is a cyclin-dependent kinase substrate including a polypeptide that contains an amino acid sequence represented by formula (1): R.sup.1P (wherein R.sup.1 represents a serine residue or a threonine residue, P represents a proline residue, represents a single bond, and the left side represents the N-terminal side), and satisfies the following (a1) and/or (b1): (a1) the second amino acid residue counting from the proline residue toward the N-terminal side in the formula (1) is an aromatic amino acid residue, and/or (b1) at least two amino acid residues from the proline residue toward the C-terminal side in the formula (1) are acidic amino acid residues.

A protein crystal comprising a first protein crystal having available space in the lattice, wherein a second protein crystal and a moiety can be accommodated in the available space in the lattice. The first and second proteins are co-expressed from one or more nucleic acid constructs. In a preferred embodiment, the first protein is the p21-activated kinase PAK4, the second protein is the PAK4 kinase inhibitor Inka1, and the moiety comprises a reporter molecule such as fluorescent proteins or tags and is fused to the iBox or iBox-C or Inka1. Preferably the crystal is formed in cellulo. Also provided is a fusion protein comprising the first protein and the second protein, wherein upon crystallisation the second protein fits within the available space in the lattice of the first protein, along with the moiety. Methods for producing the protein crystal are also disclosed.

Novel CDKL5 enzyme variants are provided, as well as fusion proteins comprising full-length CDKL5 polypeptides or CDKL5 variants. Such fusion proteins can include cell-penetrating polypeptides and optionally comprising a leader signal polypeptide and/or tags. Also provided are methods of producing such CDKL5 variants and fusion proteins, as well as pharmaceutical compositions, methods of treatment, and uses of such recombinant proteins.

Disclosed herein are compositions and formulations containing a TATk-CDKL5 fusion protein. Also disclosed are methods of producing a TATk-CDKL5 fusion protein from vectors containing a TATk-CDKL5 cDNA and methods of transducing cells with the vectors containing a TATk-CDKL5 cDNA and the TATk-CDKL5 fusion protein

The present invention relates to compounds and methods for inhibiting CDK5 or the CDK5 pathway for treating long QT syndrome (LQTS), and in particular Timothy Syndrome (TS). Additionally, the invention relates to small molecule and gene therapy based therapies and combinations for treating Timothy Syndrome (TS), and related channelopathies.

The present disclosure provides methods for inducing cell cycle reentry of postmitotic cell. The present disclosure further provides cells and compositions for treating diseases, such as cardiovascular diseases, neural disorders, hearing loss, and diabetes.

The present disclosure provides methods for inducing cell cycle reentry of postmitotic cell. The present disclosure further provides cells and compositions for treating diseases, such as cardiovascular diseases, neural disorders, hearing loss, and diabetes.

A method of determining sensitivity to cancer treatment includes the step of determining the presence of overexpression of MYC in a biological sample from a patient suffering from cancer, wherein the presence of overexpression of MYC indicates a sensitivity to a treatment by a CDK9 inhibitor and wherein the cancer is selected from the group consisting of carcinoma, leukemia, and lymphoma.

A method of sensitizing cancer to immunotherapy in a subject in need thereof includes administering to the subject a therapeutically effective amount of a CdK5 inhibitor to suppress immune checkpoint PD-L1.

Disclosed herein are systems, compositions and methods for using a split dCas protein system to modify the epigenetic profile of a gene of interest. The systems, compositions, and methods are useful for modifying the epigenetic profile of a particular gene within a cell, based on the discovery that effective expression of a larger-sized recombinant protein can be successfully achieved using two separate expression cassettes each encoding a half of the protein fused with a half of an intein, utilizing the unique feature of an intein system to ultimately rejoin the two halves to form one larger fusion protein with the intein spliced out.