The present invention refers to a fusion protein or a protein complex comprising a DNA binding protein (DnaBP), a nucleobase modifying protein (NMP), and a Base Excision Repair associated protein (BERAP. Also, described herein are a method of replacing a cytosine with a guanine on a DNA strand in a cell and a method of treating a subject having or suspected of having a disease or disorder.

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.

Mutant mono ADP-ribose-polymerases (mono-PARP) proteins and small molecule compound substrates specific for the mutant mono-PARP proteins as well as methods of using these compositions to identify protein targets of the mono-PARPs and to screen for antagonists of the mono-PARPs are described.

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.

Provided is a method for tumor treatment, comprising administering immune effector cells and a PARP inhibitor to an individual suffering from a tumor, the immune effector cell expresses a receptor for identifying a tumor antigen. Further provided is a kit for tumor treatment.

The invention provides methods and compositions for enhancing the efficacy of cancer therapies through modulation of BAL1 and/or BBAP. Also provided are methods for predicting the efficacy of cancer therapies or treating cancer in a subject through modulation of BAL1 and/or BBAP. Further provided are methods for identifying compounds that are capable of modulating BAL1-BBAP complexes.

Provided is a class of peptides which are useful for modulating the activity of poly (ADP-ribose) polymerase (PARP) and in particular for the treatment of cancer. The peptides include an active group and a cassette for delivering the active group to a cell. Also provided are peptides having an anionic group which is believed to act as a competitive inhibitor of proteases which cleave PARP.

Provided herein are methods of treating cancer comprising administering a PARP inhibitor which may be combined with a BRD4 inhibitor. In one embodiment, the present disclosure provides a method for treating cancer in a subject comprising administering an effective amount of a poly-ADP-ribose polymerase (PARP) inhibitor in combination with a bromodomain-containing protein 4 (BRD4) inhibitor to the subject. In some aspects, the administration of the PARP inhibitor and BRD4 inhibitor results in greater reduction in tumor growth or greater reduction in tumor mass relative to administration of PARP inhibitor or BRD4 inhibitor alone.

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 meso thelioma. 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.

The invention relates to compositions and methods for inhibiting macrophage activation via modulating PARP9 and/or PARP14 expression or activity, such as small molecules, RNAi and antibodies.