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.

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.

Disclosed herein are compositions and formulations containing a TATκ-CDKL5 fusion protein. Also disclosed are methods of producing a TATκ-CDKL5 fusion protein from vectors containing a TATκ-CDKL5 cDNA and methods of transducing cells with the vectors containing a TATκ-CDKL5 cDNA and the TATκ-CDKL5 fusion protein. Also disclosed are uses of TATκ-CDKL5 fusion proteins for treating CDKL5 deficiencies by systemic or intravenous administration of the fusion proteins.

Provided herein are compositions and methods for treating or preventing metabolic disorders. In particular, provided herein are compositions, methods, and uses of Cyclin-dependent Kinase 6 (CDK6) inhibitors for treating and preventing metabolic diseases (e.g., type II diabetes, obesity, metabolic syndrome, elevated blood pressure, cardiovascular diseases, elevated fasting plasma glucose, and high serum triglycerides).

The present invention relates to compositions and methods for detecting CDK4/6 response and resistance.

A fusion protein including a Cas9 protein and a modifying peptide that modifies the Cas9 protein, in which the modifying peptide includes: a peptide composed of the amino acid sequence described in SEQ ID NO: 29; or a peptide composed of an amino acid sequence in which one or several amino acids are deleted, substituted, or added in the amino acid sequence described in SEQ ID NO: 29 and having activity to localize the Cas9 protein in the nucleus by forming a fusion protein with the Cas9 protein.

The present invention relates to compositions and methods for detecting CDK4/6 response and resistance.

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.

The disclosure provides polypeptides comprising an engineered p27, or a fragment thereof such polypeptides may be used to form trimeric protein complexes with a cyclin-dependent kinase 4 (Cdk4) (or a variant thereof) or Cdk6 (or a variant thereof), and a cyclin D (CycD) or a variant thereof.

The disclosure provides polypeptides comprising an engineered p27, or a fragment thereof. Such polypeptides may be used to form trimeric protein complexes with a cyclin-dependent kinase 4 (Cdk4) (or a variant thereof) or Cdk6 (or a variant thereof), and a cyclin D (CycD) or a variant thereof.