CRISPR-Cas systems have, over the years, emerged as indispensable tools for Genetic interrogation in contexts of clinical interventions, elucidation of genetic pathways and metabolic engineering and have pervaded almost every aspect of modern biology. Within this repertoire, the nervous system comes with its own set of perplexities and mysteries. Scientists have, over the years, tried to draw up a clearer genetic picture of the neuron and how it functions in a network, mainly in an endeavor to mitigate diseases of the human nervous system like Alzheimer’s, Parkinson’s, Huntington’s, Autism Spectrum Disorder (ASD), etc. With most being progressive in nature, these diseases have plagued mankind for centuries. In spite of our immense progress in modern biology, we are yet to get a grasp over these diseases and unraveling their mechanisms is of utmost importance. Before CRISPR-Cas systems came along, the elucidation of the complex interactome of the mammalian nervous system was attempted with erstwhile existing electrophysiological, histological and pharmacological techniques coupled with Next Generation Sequencing and cell-specific targeting technologies. Zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), imparted excellent sequence specific DNA targeting capabilities but came with their huge baggage of extensive protein engineering requirements, which practically rendered them unsuitable for high throughput exercises. With the discovery of Clustered Regularly Interspaced Palindromic Repeats (CRISPR) and CRISPR Associated proteins(CAS) systems by Ishino (1987), the era of extensive custom made endonuclease targeting was ushered in. For the first time in 2012, Jinek et al. (2012) repurposed the CRISPR-Cas mediated bacterial immune system for customizable mammalian gene editing. The CRISPR-Cas technology made it possible to easily customize Cas9 endonucleases to cleave near specifically targeted sequences, thereby facilitating knock-ins or knock-outs, silencing or activating or editing any gene, at any locus of the genome, both at the base-pair level or at the epigenetic level. With this enhanced degree of freedom, decrypting the nervous system and therapeutic interventions for neuropathies became significantly less cumbersome an exercise. Here we take a brisk walk through the several endeavors of research that show how the humble bacteria’s CRISPR-Cas system gave us the “nerves” to “talk” to our nerves with ease.© 2021 Elsevier Inc. All rights reserved.
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