Gammaretroviral vectors were the first viral gene-therapy vectors to enter clinical trials and remain in use. One potential hazard associated with the use of such vectors is the presence of replication-competent retroviruses (RCR) in the vector preparations – either as a result of: 1) recombination events between the plasmids used for vector production, 2) interactions between the plasmids and endogenous retroviral sequences in the packaging cell lines, or 3) as a result of contamination in the laboratory.
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.
Molecular imaging is a disease-specific targeting modality that promises much more accurate diagnoses of serious diseases such as cancer and infections. Agents are being continually developed with a view to clinical translation, with several such therapies requiring measurement of very small doses. Currently, there is no way of accurately measuring small amounts of radioactivity used in many pre-clinical tracer studies, as on-the-market commercial dose calibrators measure at too high a dose range, typically at 10-1000 µCi and higher.
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:
The ability to hold and transport tissue, especially needle biopsies in a pre-defined and controlled environment is critical for the preservation of biopsy samples in downstream analytic applications. Currently, tissue specimens are placed in open containers with variable, poorly controlled solutions applied to them, often in less than sterile conditions. Evaluation of the tissue by examination through a stereoscope or similar approaches to determine adequacy is limited and requires manipulation of the tissue that can further damage the tissue.
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.
Melanoma is a particularly aggressive form of cancer primarily caused by over-exposure to sunlight. Although melanoma can strike at any age, the malignancy disproportionately impacts persons of advanced age, as these individuals often have decades of repeated exposure to harmful levels of ultraviolet radiation. Scientists at NIH among others have clarified the link between advanced melanoma and other malignancies and expression of SPANX-B.