Topoisomerase 1B (TOP1) is an enzyme that relieves the torsional strain in DNA. To relieve the torsional strain, TOP1B cleaves one strand of DNA and forms a transient complex called a TOP1-DNA covalent cleavage complex (TOP1cc). TOP1 inhibitors – such as camptothecin – stabilize the TOP1cc and prevent relegation of the broken DNA which, when encountered by replication and transcription machinery, triggers cell death. The DNA damage generated by the TOP1cc can be repaired by several pathways, including tyrosyl-DNA phosphodiesterase 1 (TDP1) pathway. 

The promise of RNA interference based therapeutics is made evident by the recent surge of biotechnological drug companies that pursue such therapies and their progression into human clinical trials. The present invention discloses novel RNA  and RNA/DNA nanoparticles including  multiple siRNAs, RNA aptamers, fluorescent dyes, and proteins. These RNA nanoparticles are useful for various nanotechnological applications.

IFN-gamma and IL-10 are cytokine signaling molecules that play fundamental roles in inflammation, cancer growth and autoimmune diseases.  Unfortunately, there are no specific inhibitors of IFN-gamma or IL-10 on the market to date.

Scientists at the National Cancer Institute's Molecular Targets Laboratory have discovered that Cnidarins as a novel class of highly potent proteins capable of blocking the HIV virus from penetrating T-cells. Cnidarins were found in a soft coral collected in waters off Australia's northern coast. Cnidarins can block virus fusion/entry but do not block viral attachment. In addition, Cnidarins do not have lectin-like activity and therefore possibly a unique mechanism of action.

Thalidomide and its close analogs (lenalidomide and pomalidomide) are widely used to treat a variety of diseases, such as multiple myeloma and other cancers as well as the symptoms of several inflammatory disorders. However, thalidomide is known for its teratogenic adverse effects when first clinically introduced in the 1950s, and is associated with drowsiness and peripheral neuropathy. Hence, there is intense interest to synthesize, identify and develop safer analogs. 

Advanced colorectal carcinoma is currently incurable, and new therapies are urgently needed. Ephrin (Eph) receptors are a clinically relevant class of receptor tyrosine kinases. Related signaling pathways are associated with oncogenesis of a number of cancers. NCI investigators found that phosphotyrosine-dependent Eph receptor signaling sustains colorectal carcinoma cell survival, thereby uncovering a survival pathway active in colorectal carcinoma cells.

The National Cancer Institute, Cancer and Inflammation Program seeks parties interested in collaborative research to further co-develop inhibitors of STAT proteins for the treatment of cancer.

Researchers at NIH/NICHD have identified approximately 200 proteins as candidate molecules (leads) that “fine tune” T cell receptor (TCR) signaling. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) seeks partners to collaborate on in vitro studies to validate these potential immunomodulators and to conduct in vivo studies in a murine cancer model to determine the effects of ligands (e.g. antibodies) to the proteins to determine their effect on the immune response to cancer cells.

Mesothelioma is an aggressive cancer covering anatomic surfaces (e.g. lining of the lungs, heart, abdomen, etc.) that resists multi-modality therapies. Regional recurrence of mesothelioma from residual tumor cells prevents long-term benefits after surgical resection. Furthermore, there is no clinical consensus on intracavitary adjuvants that are effective in extending the tumor reduction effect of surgery.

T cells with T cell receptors (TCRs) for cancer-specific antigens are used for adoptive cell therapy (ACT), wherein a patient’s T cells are redirected against their own cancer. However, these isolated T cells may require further ex vivo manipulation to enhance their anti-tumor activity. The ex vivo manipulation of these T cells, or the selection of less functionally inert T cells, and genetic insertion of tumor specific TCRs may circumvent these limitations.