Disclosed is a cyclin-dependent kinase substrate including a polypeptide that contains an amino acid sequence represented by formula (1): R.sup.1-P (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.

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 provides compositions for RNA interference and methods of use thereof. In particular, the invention provides small interfering RNAs (siRNAs) having modification that enhance the stability of the siRNA without a concomitant loss in the ability of the siRNA to participate in RNA interference (RNAi). The invention also provides siRNAs having modification that increase targeting efficiency. Modifications include chemical crosslinking between the two complementary strands of an siRNA and chemical modification of a 3 terminus of a strand of an siRNA. Preferred modifications are internal modifications, for example, sugar modification, nucleobase modification and/or backbone modifications. Such modifications are also useful, e.g., to improve uptake of the siRNA by a cell. Functional and genomic and proteomic methods are featured. Therapeutic methods are also featured.

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.

The oligonucleotide compositions of the present invention make use of combinations of oligonucleotides. In one aspect, the invention features an oligonucleotide composition including at least 2 different oligonucleotides targeted to a target gene. This invention also provides methods of inhibiting protein synthesis in a cell and methods of identifying oligonucleotide compositions that inhibit synthesis of a protein in a cell.

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.

Provided herein are methods for increasing telomere length comprising contacting a cell with an agent that activates the ataxia telangiectasia mutated (ATM) kinase pathway or a cyclin dependent kinase pathway, thereby elongating telomeres in the cell. Also provided is a method for treating disorders such as cancer and telomere syndromes.

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 oligonucleotide compositions of the present invention make use of combinations of oligonucleotides. In one aspect, the invention features an oligonucleotide composition including at least 2 different oligonucleotides targeted to a target gene. This invention also provides methods of inhibiting protein synthesis in a cell and methods of identifying oligonucleotide compositions that inhibit synthesis of a protein in a cell.

The present invention provides an assay that identifies genes required for telomerase-dependent telomere elongation by measuring the de novo telomere addition at a single chromosome.