Feb 19, 2019 Last Updated 1:28 PM, Feb 18, 2019

Baby gene edits could affect a range of traits

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Harnessing the potential of gene editing-based therapies has been one of the long sought-after dreams of biology and medicine. New techniques such as CRISPR and ZFP, though still in need of being refined, have opened the possibility of manipulating genomes and, for example, target specific disease-associated genes. While the perspective of modifying organisms in order to make them less susceptible to certain conditions, either pathophysiological or infective, represents a rather fascinating scenario, many think that this approach still has to deal with our very limited knowledge of the way gene products work in the context of a complete organism, in relation with the other 21.000 protein-coding genes extimated to date, with the huge non-coding part of the genome and, quite importantly, environmental variables (a good example of this complexity is represented by the fact that less than a 2% DNA divergence accounts for the phenotypic differences existing between humans and chimps). As a matter of fact we might be able to modify human genes, but our knowledge of the full spectrum of effects exerted by a certain DNA sequence on living organisms is often scarce, and seldom predictable. It is no surprise, thus, that scientific comunity was profoundly shaken, a few weeks ago, when chinese scientist He Jiankui claimed that he had made the first couple of gene-edited twin babies carryinga mutation for CCR5 chemochine receptor that make them, theoretically, immune to HIV infection.

 

Dr He introduced, in the twins' genome, a known mutation for CCR5 gene that is associated with reduced susceptibility to HIV infection. However, quite importantly, this same gene has been associated, along the years, with other functions: indeed, CCR5 is a chemochine receptor that is involved in many immune defense and several studies highlighted its crucial role in the protection against other pathogen infections such as, influenza, west-nile virus or tick-borne diseases, as well as in the outcome of some neurodegenerative conditions (e.g. multiple sclerosis); in light of this, many immunologist and infectivologists agree in saying that CCR5 deficiency is far from being a de facto benign condition. On the other hand, CCR5 importance might go way beyond its role in immunity: indeed, surprisingly, CCR5-KO mice display enhanced learning. Together, all of these evidences show how the pleiotropic role of most of genes -and their products- makes the prediction of their outcome on health and disease very difficult, and highlights the limits, at least to date, of a gene-editing strategy based on the simplistic intervention on a single locus which is believed to intervene on a only one biological function. 

Source: Nature website

Last modified on Friday, 14 December 2018 13:05
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