The field of gene therapy is striving more than ever to define a path to the clinic and the market. Twenty gene therapy products have already been approved and over two thousand human gene therapy clinical trials have been reported worldwide. These advances raise great hope to treat devastating rare and inherited diseases as well as incurable illnesses. Understanding of the precise pathomechanisms of diseases as well as the development of efficient and specific gene targeting and delivery tools are revolutionizing the global market. Currently, human cancers and monogenic disorders are indications number one. The elevated prevalence of genetic disorders and cancers, clear gene manipulation guidelines and increasing financial support for gene therapy in clinical trials are major trends. Gene therapy is presently starting to become commercially profitable as a number of gene and cell-based gene therapy products have entered the market and the clinic. This article reviews the history and development of twenty approved human gene and cell-based gene therapy products that have been approved up-to-now in clinic and markets of mainly North America, Europe and Asia.

It has been suggested that mood disorders and depressive status may be accompanied by lowered zinc status in the body, and adequate consumption of zinc increases a general perceived well-being. The main objective of this study was to assess the correlation between serum zinc concentrations and dietary zinc intakes with depression scores in university female students. In the first phase, Beck's depression questionnaire was applied in a random sampling of 308 selected 20-25-year-old female students (one third of total students in Ahvaz Jondi-Shapour University of Medical Sciences Golestan dormitories) to assess the major depressive disorder (MDD) scales. Then, in the second phase, 23 students who identified as having moderate and severe depression were selected as the case group, and 23 healthy age matched were chosen as the controls. Each of them completed a 12-item semiquantitative food frequency questionnaire containing the main food sources of zinc in the usual dietary patterns and also a 24-h food recall questionnaire to assure the daily zinc intakes. Daily zinc intakes were obtained by multiplying each portion size by its zinc content using food tables. A 5-ml blood sample was taken for further serum zinc status using flame atomic absorption spectrophotometry technique. Pearson's r was used to show the correlation between quantitative variables. Both daily zinc intake and serum zinc concentrations of MDD group were about two thirds of healthy index (p < 0.01). Depressed individuals used to eat lower servings of red meats and chicken as the main food sources of zinc in students' usual diets (p < 0.001). Consumption of other foods as the sources of zinc was not significantly different in two groups. A linear significant correlation between dietary zinc intakes and its serum levels was seen in samples (r = 0.62; p < 0.001) and MDD students (r = 0.55; p < 0.001). There was a linear inverse correlation between Beck questionnaire scores and serum zinc concentrations in all of the investigated students(r = -0.65; p < 0.001) and MDD girls (r = -0.71; p < 0.001). Beck questionnaire scores and diatary zinc intakes were also inversly correlated (r = -0.58; p < 0.001). However, no statistical correlation was seen between these two variables in MDD cases. In depressed female students, dietary zinc intake is correlated to its serum concentrations; however, the serum zinc levels are inversely correlated to depression scales. Consumption of the main dietary sources of zinc such as red meats and chicken should be encouraged in young depressed girls.

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Currently, 33 gene‐therapy drugs/products have been approved in the clinic. Over 3000 completed and ongoing clinical gene therapy trials have been reported worldwide. The development/maturation of tools for gene manipulation and gene delivery, as well as molecular advances in the diagnosis of genetic diseases, have played a central role in gene therapy, which have greatly revolutionized the field. Versatile and diverse genetic tools for gene manipulations and deliveries, with the possibility of short and long‐term effects, are vital advantages of gene therapy tools, paving the road for the development of new therapies. However, efficacy and safety concerns, immune system responses, laborious approaches for developing and manufacturing, unknown gene‐therapy drug interactions with the host and the high cost of drugs/products, are significant barriers in gene therapy. Here, the authors review the attempts for engineering of the gene manipulations that have been undertaken in the last three decades and used in clinical trials focusing on 1) gene‐editing platforms, 2) viral gene delivery systems, and 3) nonviral gene tools. In this comprehensive review, the principles of these gene manipulation tools as well as advances and barriers for their application in modern therapies are discussed. Furthermore, trends and future directions in gene therapy are discussed.

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