CRISPR-Cas: Revolutionising genome engineering

The ability to permanently alter or repair the human genome has been the subject of a number of science fiction films, but with the recent advent of several customisable sequence-specific endonuclease technologies, genome engineering looks set to become a clinical reality in the near future. This article discusses recent advancements in the technology called ‘clustered regularly interspaced palindromic repeat (CRISPR)-associated genes’ (CRISPR-Cas), the potential of CRISPR-Cas to revolutionise molecular medicine, and the ethical and regulatory hurdles facing its application

Cell and gene therapies at the forefront of innovative medical care: Implications for South Africa

The fields of cell and gene therapy are moving rapidly towards providing  innovative cures for incurable diseases. A current and highly topical  example is immunotherapies involving T-cells that express chimeric antigen receptors (CAR T-cells), which have shown promise in the treatment of leukaemia and lymphoma. These new medicines are indicative of the changes we can anticipate in the practice of medicine in the near future. Despite their promise, they pose challenges for introduction into the healthcare sector in South Africa (SA), including: (i) that they are  technologically demanding and their manufacture is resource intensive; (ii) that the regulatory system is underdeveloped and likely to be challenged by ethical, legal and social requirements that accompany these new therapies; and (iii) that costs are likely to be prohibitive, at least initially, and before economies of scale take effect. Investment should be made into finding novel and innovative ways to introduce these therapies into SA sooner rather than later to ensure that SA patients are not excluded from these exciting new opportunitie

Thrombospondin-1 is downregulated by anoxia and suppresses tumorigenicity of human glioblastoma cells.

Angiogenesis, the sprouting of new capillaries from preexisting blood vessels, results from a disruption of the balance between stimulatory and inhibitory factors. Here, we show that anoxia reduces expression of thrombospondin-1 (TSP-1), a natural inhibitor of angiogenesis, in glioblastoma cells. This suggests that reduced oxygen tension can promote angiogenesis not only by stimulating the production of inducers, such as vascular endothelial growth factor, but also by reducing the production of inhibitors. This downregulation may significantly contribute to glioblastoma development, since we show that an increase in TSP-1 expression is sufficient to strongly suppress glioblastoma cell tumorigenicity in vivo

The prototypes of tobacco users scale (Potus) for cigarette smoking and e-cigarette use: Development and validation

Endorsing prototypes of cigarette smokers predicts cigarette smoking, but less is known about prototypes of users of other tobacco products. Our study sought to establish the reliability and validity of a measure of prototypes of smokers and e-cigarette users. Participants were from a national survey of smokers and non-smokers (n = 1414), a randomized clinical trial (RCT) of adult smokers (n = 2149), and adolescent children of adults in the trial (n = 112). The Prototypes of Tobacco Users Scale (POTUS) has four positive adjectives (cool, sexy, smart, and healthy) and four negative adjectives (disgusting, unattractive, immature, and inconsiderate) describing cigarette smokers and e-cigarette users. Confirmatory factor analyses identified a two-factor solution. The POTUS demonstrated strong internal consistency reliability in all three samples (median α = 0.85) and good test–retest reliability among adults in the RCT (median r = 0.61, 1–4 weeks follow-up). In the RCT, smokers more often agreed with negative prototypes for smokers than for e-cigarette users (mean = 2.03 vs. 1.67, p < 0.05); negative prototypes at baseline were also associated with more forgoing of cigarettes and making a quit attempt at the end of the trial (Week 4 follow-up). The POTUS may be useful to public health researchers seeking to design interventions that reduce tobacco initiation or cessation through the manipulation of tobacco user prototypes

The genetics of obesity: the role of the melanocortin 4 receptor

Obesity, which is described clinically by a body mass index (BMI) of > 30 kg/m2 is increasing at an alarming rate, and is recognised as a chronic disease by the World Health Organization (WHO). This epidemic decreases life expectancy, and its prevalence is increasing within the global paediatric and adult populations in most African countries, South Africa included. Research has revealed the importance of the genetic component of obesity, with much emphasis to date having been placed on monogenic disease. Polymorphisms within the gene encoding for the melanocortin-4 receptor (MC4R), a hypothalamic receptor with the primary function of regulating food intake, are a significant cause of severe human obesity. Studies have shown a correlation between the degree of MC4R dysfunction and the severity and age of onset of obesity. The accepted mode of inheritance for MC4R mutations is co-dominance with modulation of penetrance and expressivity, which would explain why homozygous carriers are more obese than heterozygotes. MC4R mutation frequency is also dependent on the ethnicity of the population. The use of genetic markers for diagnostic strategies and as predictors of therapeutic outcome will be of importance in the future management of obesity.Keywords: genetics; obesity; melanocortin 4 recepto

Ethical considerations in the application of cell and gene therapies in children

Rapidly evolving fields such as cell and gene therapies that involve state-of-the-art technology hold out possibilities that may be ahead of what ethics, guidelines and the law have considered. This results in a regulatory lag. Furthermore, ethical and legal considerations are often debated in real time as issues pertaining to these technologies that were previously not considered begin to come to the fore. Finding the appropriate balance between facilitating potential therapeutic gains and ensuring the safety interests of recipients of the new treatments requires close attention, especially for minors. This vulnerable population frequently has off-label treatment prescribed on the basis of extrapolation of clinical trial data derived from adults, which is ethically and scientifically questionable. In this article we discuss how best to maintain ethical integrity while introducing innovative cell and gene therapies to minors. We advocate that clinical trials of promising innovative therapies should be designed so that testing in adults is followed as soon as possible by testing in minors, given the impressive gains that have recently been reported

Evaluation of TickGARD(PLUS), a novel vaccine against Boophilus microplus, in lactating Holstein-Friesian cows

The effects of vaccination with the Bm 86 vaccine TickGARDPLUS against infestation with cattle tick (Boophilus microplus) and of holding cattle on a feedpad until 09:00 hours after the morning milking was tested on 40 mid lactation Holstein cattle using a factorial design. Vaccination resulted in a 56% reduction in tick numbers in the field over one generation, and a 72% reduction in laboratory measures of the reproductive efficiency of ticks. The liveweight gain of vaccinated cattle over 27 weeks was 18.6 kg higher than that of controls, and vaccinated cattle tended to have lower somatic cell count in milk (SCC). There were no other significant differences in measures of production. Cattle kept on the feedpad after the morning milking carried 26% more ticks than those returned immediately to their paddocks

Endothelial cells of the microvasculature express epidermal fatty acid-binding protein (E-FABP)

Item does not contain fulltex