FM DECEMBER 2018 ISSUE - digital edition

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essay CRISPR STEALS THE SHOW IN MOLECULAR LABS Industries have started exploiting the new gene editing tool for various purposes CONFERENCE 2018 competition Sara Anisa George, Jr Research Fellow, Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India SARA ANISA GEORGE The term ‘CRISPR technology’ has of late, been making waves both within and outside the scientific community. The potential power of this novel and ground-breaking technology to completely change the face of science and give scientists the ability to play God has sent the world into a tizzy. First discovered in Escherichia coli by Yoshizumi Ishino in 1987 and later by Francisco Mojica in Haloferax mediterranei in 1992 (Mojica et al, 1993), Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) were then identified in other bacteria. In-depth studies recognised the role of CRISPRs and their associated Cas enzymes in the prokaryotic adaptive immune response against invading viruses. Further research by other groups into this newly discovered bacterial anti-viral response led to the elucidation of its mechanism as an RNA-guided editing tool that generates double-stranded breaks in target DNA. However, it was only after the report of the ability of the Cas9- CRISPR combination to edit nearly any chosen sequence of DNA, by the labs of Emmanuelle Charpentier and Jennifer Doudna in 2012 (Jinek et al, 2012) that the possibility of using this technology as a gene-editing tool in higher eukaryotes was considered. This theory was proven by the research groups of Feng Zhang and George Church in human cell-lines, the following year (Cong et al, 2013; Mali et al, 2013). This technology has been gaining popularity at an exceedingly increased pace and has now become a staple in most molecular biology laboratories around the world, which has led to the development of DUE TO ITS RELATIVE SIMPLICITY AND EASE OF USE CRISPR/CAS9 AND ITS DERIVED TECHNOLOGIES HAVE FOUND USES IN THE FIELD OF MEDICINE AND HEALTHCARE several modifications to the original CRISPR components based on the downstream use, enabling more precision and specificity in gene editing properties. Impact in medicine Due to its relative simplicity and ease of use in comparison to previously known genome editing tools such as RNAi, zinc-finger nucleases (ZFNs) 94 / FUTURE MEDICINE / DECEMBER 2018
and transcription-factor like effector nucleases (TALENS), CRISPR-Cas9 and its derived technologies have found uses in several areas of modern science, but its greatest impact has been in the field of medicine and healthcare. Initial studies focused on in-vitro research in animal cell-lines and embryos to study genes involved both in normal metabolism as well as in disease development (Wang et al, 2014; Zhou et al, 2014; Roy et al, 2015; Zhang Y et al, 2018; Van Treuren et al, 2018; Ojalill et al, 2018). However, due to the rapid pace of development of this technology, at present, several in-vivo studies are already in progress to develop CRISPR-based strategies that can be used in the treatment of previously incurable genetic disorders. Some of the examples of the use of this technology include the treatment of disease models of Huntington’s disease, phenylketonuria, Duchenne’s muscular dystrophy, etc.(Yang et al 2017; Villiger et al, 2018; Amoasii et al, 2018). Gene editing studies have not been restricted to metabolic disorders, in fact, a number of research groups have transferred their focus on inventing techniques to control the spread of infectious diseases such as AIDS, malaria, candidiasis, herpes, etc. by either manipulating the pathogen itself or its transmitting vector (Gantz et al, 2015; Vyas et al, 2015; Hammond et al, 2016; Van Dieman et al, 2016; Kaminski et al, 2016; Yin et al, 2017). The CRISPR pioneering laboratories of Doudna at the University of California and Zhang at the Massachusetts Institute of Technology have utilized their expertise to design kits that will ensure more precise and sensitive for pathogen detection and disease diagnosis (Myhervold et al, 2018; Chen et al, 2018). In addition, other labs and start-up industries have also started exploiting this new technology for similar purposes (Koo et al, 2018). Agri and food industry The advances in the field of agriculture and in the food industry are not far behind. With a steady rise in populations especially in the developing parts of the world, there has been an increasing demand for the production of high-quality varieties of crop plants, and agricultural scientists have till date relied on traditional breeding methods to meet this need. CRISPR-derived methods have been used to generate high yielding, disease resistant and nutrient-rich crops that cater to the CRISPR-DERIVED METHODS HAVE BEEN USED TO GENERATE HIGH YIELDING, DISEASE RESISTANT AND NUTRIENT-RICH CROPS THAT CATER TO THE NEEDS OF THE MASSES needs of the masses (Jacobs et al, 2015; Tashkandi et al, 2018; Shimatani et al, 2018; Chen et al, 2018; Zhang et al, 2018). The use of CRISPR in the food industry is as yet in its early stages especially due to hesitance from the general public to adopt this novel technology, but further developments are believed to bring about a revolution in the way we perceive food. Like all good things have a downside to them, similarly, there have been concerns with regard to the indiscriminate use of CRISPR for gene editing. Studies are already underway to attempt editing human embryos for the purpose of developing disease-free humans (Liang et al, 2015; Kang et al, 2016). CRISPR’s reported off-target editing effects also prove to be an enormous disadvantage due to the possibility of generating undesirable mutants that may have serious effects in the long run, especially if used in humans. What this new technology has in store for mankind will soon become a reality. DECEMBER 2018 / FUTURE MEDICINE / 95
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editor’s note Dear Doctor, DECEMB
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58 HEALTH INSURANCE FEWER EXCLUSION
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A medical science and news magazine
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pro bono technical and scientific r
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EU, US experts reach a consensus on
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DR SUMIT GHOSHAL Students joining t
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“CONCEPT FOR NEW CURRICULUM WAS D
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entitlement based scheme, the prope
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in 2017, nearly 5,000 new infection
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the therapeutic and preventive bene
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probably allow people to achieve th
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investigational prodrug of temsavir
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drug resistance THREAT OF RESISTANT
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