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Cytidine analogs remain an area of active drug discovery and development, with five FDA approved drugs for the treatment of acute myeloid leukemia (AML). Two of these drugs, azacitidine (Vidaza®) and decitabine (Dacogen®), which were approved for myelodysplastic syndromes in 2004 and 2006, respectively, inhibit the DNA maintenance methyltransferase DNMT1. Because of the general toxicity of azacitidines, other nucleoside analogs are favored as therapeutics.

The tumor protein p53 is a cell cycle regulator. It responds to DNA damage by triggering the DNA repair pathway and allowing cell division to occur or inducing cell growth arrest, cellular senescence, and/or apoptosis. p53 therefore acts as a tumor suppressor by preventing uncontrolled cell division. However, mutations in p53 that impair its cell cycle regulatory functions can induce uncontrolled cell division leading to cancer.

Hematopoietic and pluripotent stem cells can be differentiated into T cells with potential clinical utility. Current approaches for in vitro T cell production rely on Notch signaling and artificial mimicry of thymic selection. However, these approaches result in unconventional or phenotypically aberrant T cells; which may lead to unpredictable behavior in clinical use. Thus, there exists a need for improved methods of generating conventional T cells in vitro from stem cells.
 

Peptides corresponding to transmembrane domains of a number of integral proteins were discovered to spontaneously self-assemble in aqueous solutions into stable and remarkably uniform nanoparticles.  Researchers at the NCI’s Cancer and Inflammation Program have developed fully synthetic, peptide-based, virus-like nanoparticles capable of delivering cytotoxic, radioactive, and imaging agents. 

Structure and function of tumor-target self-assembling particles:

Virus entry into a susceptible host cell is the first step in the formation of all viral diseases. Controlling viral infections by disrupting viral entry is advantageous for antibody-mediated neutralization by the host’s immune system and as a preventive and therapeutic antiviral strategy. Plant-derived carbohydrate-binding proteins (lectins) have emerged as a new class of antiviral biologics by taking advantage of a unique glycosylation pattern only found on the surface of viruses.

The only currently available treatment for Menkes disease, subcutaneous copper histidinate injections, is successful only in patients with ATP7A gene mutations that do not completely corrupt ATP7A copper transport function (estimated 20-25% of affected patients) and when started at a very early age (first month of life). The combination of viral gene therapy with copper injections provides working copies of the ATP7A copper transporter into the brain, together with a source of the substrate (copper)  needed for proper brain growth and clinical neurodevelopment.

GSD-Ia is an inherited disorder of metabolism associated with life-threatening hypoglycemia, hepatic malignancy, and renal failure caused by the deficiency of glucose-6-phosphatase-alpha (G6Pase-alpha or G6PC). Current therapy, which primarily consists of dietary modification, fails to prevent long-term complications in many patients, including growth failure, gout, pulmonary hypertension, renal dysfunction, osteoporosis, and hepatocellular adenomas (HCA).

GSD-Ia is an inherited disorder of metabolism associated with life-threatening hypoglycemia, hepatic malignancy, and renal failure caused by the deficiency of glucose-6-phosphatase-alpha (G6Pase-alpha or G6PC). Current therapy, which primarily consists of dietary modification, fails to prevent long-term complications in many patients, including growth failure, gout, pulmonary hypertension, renal dysfunction, osteoporosis, and hepatocellular adenomas (HCA).

Glycogen storage disease type Ib (GSD-Ib) is an autosomal recessive disorder caused by deficiencies in glucose-6-phosphate transporter (G6PT), a ubiquitously expressed endoplasmic reticulum (ER) protein that translocates G6P from the cytoplasm into the ER lumen.  Inside the ER, G6P is hydrolyzed to glucose and phosphate by either the liver/kidney/intestine-restricted glucose-6-phosphatase-α (G6Pase-α or G6PC) or the ubiquitously expressed G6Pase-β.  G6PT and G6Pase are functionally co-dependent and form the G6PT/G6Pase complexes.

The options for male contraceptives are limited. Research is ongoing to develop a male contraceptive based on hormonal activity. Testosterone is one of the hormones necessary in producing sperm.  Testosterone is absolutely required as a hormone for male fertility. Derivatives of testosterone for male contraceptives currently in clinical trials are associated with estrogenic deficiency. This deficiency can cause several issues including, but not limited to, bone density loss, risk of obesity, cardiovascular disease, and/or ineffective carbohydrate or lipid metabolism.