X-linked forms of retinitis pigmentosa (XLRP) are relatively severe blinding disorders, resulting from progressive photoreceptor dysfunction primarily caused by mutations in RPGR or RP2 gene.

Scientists at the NCI's Surgery Branch have developed anti-CD70 chimeric antigen receptors (CARs) to treat cancers. CD70 is an antigen that is expressed on a variety of human cancers such as renal cell carcinoma, glioblastoma, non-Hodgkin's lymphoma, and chronic lymphocytic leukemia. The anti-CD70 CARs are hybrid proteins consisting of a receptor portion that recognizes CD70 antigen, and intracellular T cell signaling domains selected to optimally activate the CAR expressing T cells.

GBM is the most aggressive form of brain cancer. The current standard of care against GBM is a combination of surgery, chemotherapy and radiotherapy. However, after standard treatment, the cancer usually recurs – emphasizing a need for new targets and better alternatives. A promising target is cyclin-dependent kinase 5 (CDK5), the hyperactivity of which has been shown to have a role in cancer progression. 

Ataxia telangiectasia mutated and Rad3 Related (ATR) protein kinase is essential for regulating DNA damage checkpoints during the cell cycle. ATR, is phosphorylated at threonine 1989 site (T1989) in response to DNA damage and ATR activation leads to activation of downstream substrates, signaling cascades and cell cycle arrest. ATR is a potential target for anticancer therapeutics to induce cancer cell death by inhibiting cell cycle arrest pathways in response to chemotherapeutics.

Surgery is the standard care for patients with stage I lung cancer. Despite successful surgery, 20-30% of patients will relapse. Chemotherapy can improve patient survival; however, it is controversial if early stage cancer patients should be treated with chemotherapy since, for many cases, it will harm quality of life with little therapeutic benefit.

Degeneration of retinal tissues occurs in many ocular disorders resulting in the loss of vision. Dysfunction and/or loss of Retinal Pigment Epithelium Cells (RPE) and disruption of the associated blood retinal barrier (BRB) tissue structures are linked with many ocular diseases and conditions including: age-related macular degeneration (AMD), Best disease, and retinitis pigmentosa. Engineered tissue structures that are able to replicate the function of lost BRB structures may restore lost vision and provide insight into new treatments and mechanisms of the underlying conditions. 

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.

Small molecule fluorescent probes are important tools in diagnostic medicine. Existing far-red and near-IR cyanine fluorophores (e.g. Cy5, Alexa 647, Cy7, ICG) are active in the far-red and near-range, but these agents suffer from modest quantum yields (brightness) which limit wide utility. It has been reported that the limited brightness of these fluorophores is due to an excited-state C-C rotation pathway.