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Business News/ Opinion / Online-views/  Disruptive transformation

Very few technologies in the biology space have the ability to bring about disruptive transformation and capture the imagination of scientists, clinicians, policymakers and ordinary people equally. Gene editing is one such technology that has been in the news lately for its potential applications in the realms of basic biology, biomedical sciences and agriculture. This technology holds promise not only for treatment of human diseases through correction of gene defects in cells, but also has potential for improving agricultural yields, producing disease- and pest-resistant animals and crops, and for producing organisms that can synthesize specific products of commercial or medicinal importance.

Gene editing is a type of genetic engineering in which “molecular scissors" are used to create specific modifications in DNA including insertion and deletion of DNA sequences at desired genomic locations within a cell. The gene-editing molecular toolbox includes several popular molecular scissors such as Zinc Finger Nucleases (ZFNs), transcription activator-like effector nuclease (TALENs) and clustered regularly-interspaced short palindromic repeats-Cas system (CRISPR-Cas). In general, these work by inducing site-specific breaks on DNA strands at desired locations in the genome. When such breaks are created on the DNA strand, the cell attempts to repair these breaks using its endogenous repair machinery. These repair processes are often error-prone and this results in changes in the desired locations in the DNA.

ZFNs have been around in laboratories since the mid-1990s; however, they were not efficient enough for practical application. In the last decade, ZFNs have been used to create tailored heritable changes in DNA of plants. Plants such as soyabean and maize have been modified to enhance desired traits, including herbicide tolerance, and improve seed development. TALENs and CRISPR-Cas systems are popular gene-editing tools employed by many laboratories at present. TALENs and CRISPR-Cas system have been successfully applied to engineer heritable genome modification for resistance to bacterial blight in rice and to tailor desirable traits in other plants such as sorghum, wheat and tobacco. Scientific literature abounds with examples of these gene-editing tools being applied to make site-specific gene modifications in animals such as zebrafish, rats, mice and pigs for scientific discovery. Recent advancements also include gene-edited “micropigs" for those interested in designer pigs as pets. These technologies have also been applied for generating mutations in the mosquito Aedes aegypti, the vector for chikungunya and dengue viruses and in economically important organisms such as silkworm.

Human gene therapy is another area where gene-editing techniques have been demonstrated to have potential application. These techniques have been employed for treating inherited diseases by repairing the defective gene. Recent examples include correction of a gene defect in blood-cell precursors for the treatment of sickle cell disease and X-linked severe combined immunodeficiency. With the advances in stem cell technologies, it is possible to obtain induced pluripotent stem cells (iPSCs) from patient-derived cells. Application of site-specific gene modification in such patient-derived iPSCs is an attractive option for gene therapy in future. Gene editing has also been applied for correction of mutations that cause Duchenne muscular dystrophy and cystic fibrosis. These studies present a way forward for the application of gene editing for treating human diseases. The opportunities provided by the gene-editing techniques are diverse, as demonstrated by researchers at Harvard Medical School in the US who have been successful in modifying over 60 genes in pigs with the aim of making the animal a more suitable non-human organ donor.

As with all emerging technologies, gene editing is not without limitations. Ensuring specificity of the desired genetic modification has been an important concern. Though techniques to avoid off-target gene modification have been developed and tested, these are largely in the realm of research. One has to incorporate methods to prevent off-target modifications, a critical safely net, before deploying gene editing in large-scale settings. It is also important that suitable laws are framed with foresight to bring the benefits of this technology to the common man and at the same time help prevent the accidental release of modified organisms.

For countries such as India, gene-editing techniques hold special interest as they provide a fast track to develop organisms with specific desired outcomes. Gene-editing tools can be utilized to produce desired traits in indigenous varieties of plants, for example enhancing the yield of a specific nutrient; producing disease- and pest-resistant crops; increasing the oil content of seeds etc. Similarly, the gene editing techniques have tremendous application value for obtaining desired traits in cattle, buffalo, fish and economically important insects, among others. Another area that would benefit from this technology is mosquito control and the benefits of this are immense in terms of improving healthcare in this country. In biomedical settings, gene-editing techniques will be important for treating a number of inherited diseases in India. In addition, gene editing will also be important for modelling human disease mutations. For example, at the CSIR-Institute of Genomics and Integrative Biology, New Delhi, gene editing is applied for modelling rare human genetic mutations in zebrafish for better understanding of the disease mechanism.

The authors are scientists at New Delhi-based CSIR-Institute of Genomics and Integrative Biology, a research institute.

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Updated: 16 Feb 2016, 01:30 AM IST
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