Dz13

Dz13 is an experimental treatment developed by scientists at the University of New South Wales. The drug aims to combat a range of illnesses, including skin cancer, restenosis, arthritis and macular degeneration. Trials of Dz13 were suspended in 2013. Dz13 is an experimental treatment developed by scientists at the University of New South Wales. The drug aims to combat a range of illnesses, including skin cancer, restenosis, arthritis and macular degeneration. Trials of Dz13 were suspended in 2013. Dz13 is a 10-23 DNAzyme that targets c-Jun, a transcription factor found in diseased blood vessels, eyes, lungs and joints. The treatment works by the DNA-based enzyme binding to and catalytically destroying its target messenger RNA, thereby inhibiting c-Jun expression in cells. Dz13 has underpinned the development of a library of programmable DNAzymes operable in a cellular environment. The potential of Dz13 as a therapeutic agent derives from the fact that inactivation of c-Jun can have an effect on downstream genes such as MMP-2, MMP-9, VEGF and FGF-2. Dz13 also inhibits the expression of pro-inflammatory cytokines such as TNF-alpha, interferon gamma and IL-6. Dz13 has been shown to inhibit skin cancer growth, angiogenesis and tumor angiogenesis and improve survival in mice infected with H5N1. Anti-cancer effects have been also demonstrated in models of prostate cancer, breast cancer and osteosarcoma. Clinical trials of Dz13 in patients with basal cell carcinoma commenced in Australia in 2010. In 2013 it was reported that Dz13 was safe and well tolerated after single intratumoral injection at all doses. c-Jun expression was reduced in the excised tumors of all patients injected and tumor depth decreased in the majority. This was the first report of the clinical use of a DNAzyme. The outcome of two other clinical trials evaluating DNAzymes performed in Asia and Europe were reported in 2014 and 2015, the former assessing a Epstein–Barr virus latent membrane protein 1 targeting DNAzyme and the latter a DNAzyme targeting the transcription factor GATA3 which involved 7 trial sites. In both trials, there were no adverse events due to DNAzyme. There was demonstrable efficacy noted in nasopharyngeal cancer patients injected with LMP1 DNAzyme and allergic asthma patients following GATA3 DNAzyme inhalation. In 2013, trials of Dz13 on humans were suspended, after separate allegations of scientific misconduct were raised by Dr Ying Morgan, one of the original researchers, and Professor David Vaux, a scientist at Walter and Eliza Hall Institute. Vaux raised concerns about inappropriately duplicated images published in a 2010 paper, while Morgan said the same images were misrepresentations, and that the experiments were improperly conducted. Previously in 2010, three journal papers from the laboratory of Dz13 lead researcher Professor Levon Khachigian were retracted after Vaux alleged that there were inappropriately duplicated images in them. Two investigations launched by UNSW found no misconduct, the results of the second of which were marked highly confidential. Vaux later said that a second panel of inquiry had ignored his concerns and 'were constrained by the very narrow terms of reference set by the university', while Morgan said that she was not interviewed by the second panel of inquiry.