Methods and compositions are provided for determining whether an adenocarcinoma or squamous cell carcinoma patient is likely to respond to PARP inhibitor treatment. Specifically, a method of assessing whether a patient's adenocarcinoma (AD) lung cancer subtype is terminal respiratory unit (TRU), proximal inflammatory (PI), or proximal proliferative (PP) or a patient's squamous cell carcinoma (SQ) is primitive, classical, secretory or basal is provided herein. The method entails detecting the levels of classifier biomarkers at the nucleic acid level, in an AD or SQ lung cancer sample obtained from the patient. Based in part on the levels of the classifier biomarkers, the AD lung cancer sample is classified as a TRU, PI, or PP AD sample or the SQ lung cancer sample is classified as primitive, classical, secretory or basal and a determination of whether the patient is likely to respond to PARP inhibitor treatment can be made.

The present invention relates to a method for the production of a serine ADP-ribosylated protein or peptide comprising preparing an aqueous buffered solution comprising 5 to 60 mM, preferably 10 to 60 mM of a buffer and having a pH between 5.0 and 9.0, preferably between 5.5 to 8.5, and most preferably between 6.1 to 8.3, said solution further comprising (a) 0.2 to 2.5 mM NAD.sup.+, (b) at least 50 nM, preferably 50 to 3000 nM PARP-1, PARP-2 or the PARP-1 variant E988Q, (c) at least 100 nM, preferably 100 to 5000 nM HPF1, (d) at least 10 μg/mL, preferably 10 μg/mL to 200 μg/mL sonicated DNA, said sonicated DNA preferably comprising DNA fragments of 10 to 330 bp, and (e) up to 600 μM protein or peptide, said protein or peptide comprising at least one serine, thereby generating a reaction mix, in which the protein or peptide becomes serine ADP-ribosylated.

The present disclosure relates to a method of treating arthritis by targeting Tankyrase. The methods according to the present disclosure can be advantageously used for regeneration of cartilage tissue and for treating osteoarthritis by maximizing the matrix synthesis in cartilage by inhibition of Tankyrase and regulation of other proteins related therewith.

A lentiviral vector system for expressing a lentiviral particle is disclosed. The lentiviral vector system includes a therapeutic vector, an envelope plasmid, and at least one helper plasmid. The lentiviral vector system can produce a lentiviral particle for inhibiting PARP expression in neuron cells of a subject afflicted with Parkinson's disease.

The invention relates to compositions of vault complexes containing recombinant cytokine fusion proteins that include a cytokine and a vault targeting domain, and methods of using the vault complexes to deliver the cytokines to a cell or subject, and methods for using the compositions to treat cancer, such as lung cancer.

The present invention relates to the use of an agent that inhibits the activity of an enzyme that mediates repair of a DNA strand break in the manufacture of a medicament for the treatment of diseases caused by a defect in a gene that mediates homologous recombination.

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.

Compounds for treatment of diseases having acidic or hypoxic diseased tissues and pharmaceutical compositions comprising the compounds, as well as methods for making and using the compounds and compositions.

The present invention relates to a method for producing a site-specifically serine ADP-ribosylated protein or peptide being, comprising: (a) subjecting a protein or peptide comprising or consisting of an amino acid sequence comprising two or more serines, wherein at least one serine is phosphorylated and at least one serine is non-phosphorylated, to a serine ADP-ribosylation reaction. The present invention also relates to a site-specifically serine ADP-ribosylated protein or peptide produced by the method of the invention.

The subject invention provides a pharmaceutical composition comprising an inhibitory RNA (iRNA) that mediates sequence-specific degradation of the mRNA encoding Poly (ADP-ribose) polymerase 1 (PARP1) and methods of treating cancers by administering the pharmaceutical composition to a subject in need thereof. In one embodiment, the iRNA is miR-223, particularly, miR-223-3p or a modified miR-223-3p having substitutions and/or deletions in the sequence of miR-223-3p. In another embodiment, the cancer cells comprise one or more mutations in the genes that mediate homologous recombination DNA repair, for example, BRCA1 and/or BRCA2 genes. The cancer can be breast cancer, ovarian cancer, prostate cancer, pancreatic cancer or mesothelioma. Methods of treating cancer, for example, a cancer comprising BRCA1 and/or 2 mutations, using a combination of iRNA and a second cancer therapeutic are also provided.