Genomics
References 1 Moreno, AM and Mali, P. Therapeutic Genome Engineering via CRISPR-Cas Systems, Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 2017, 9, e1380. 2 Comley, J. CRISPR Cas9: transforming gene editing in drug discovery labs, Drug Discovery World, 2016. 3 Ahmad, G and Amiji, M. Use of CRISPR/Cas9 gene-editing tools for developing models in drug discovery, Drug Discovery Today, 2018, 23, 518. 4 Mohr, SE et al. RNAi screening comes of age: improved techniques and complementary approaches, Nature Reviews Molecular Cell Biology, 2014, 15, 591.
Figure 2:CRISPR-Cas9 3D structure from Streptococcus pyogenes
4D-Nucleofector™ System is a flexible, modular system that allows for closed, scalable transfection of larger cell numbers without the need to re-opti- mise protocols. The 96-well Shuttle add-on enables medium-throughput with the system, and this can be expanded to large-scale transfection using the 4D-Nucleofector™ LV Unit. Additionally, the 384- well HT-Nucleofector™ Device is a stand-alone system that offers extremely fast plate processing times of just one minute. This high-throughput solution delivers high performance and minimal material consumption, with effective nucleofec- tion of low cell numbers down to 20,000 cells and even lower. The Nucleofector™ Devices range offers a very scalable approach for gene editing, allowing researchers to take their research in the direction they choose. Thermo Fisher Scientific is applying the power
of the CRISPR-Cas9 system to high-throughput screening applications with the Invitrogen™ LentiArray™ CRISPR libraries. The range consists of 17 gene set libraries, the complete druggable genome, as well as the whole genome. Libraries can be purchased as single or multiple gene sets, the whole genome, or fully-customised arrays. Each library comes as 96-well plates containing ready-to-use lentiviral particles, with up to four
64
gRNAs per gene target for efficient knockout. Additionally, the Invitrogen™ TrueCut™ Cas9
Protein v2 has been designed to deliver consistently high editing efficiency across a range of gene tar- gets and cell types, including standard, immune, primary and stem cells. The efficiency achieved using this second-generation protein is among the highest of commercially-available Cas9 nucleases.
The future of the field While a small subset of diseases may be attributed to a single genetic mutation, two decades of genetic sequencing efforts suggest that they are the low-hanging fruit. The majority of diseases are multimodal, with multiple mutations in the protein-coding or non-coding genome. To identify the next generation of therapeutic targets, it seems likely that a more systems-based approach will be required. “The rapid growth in genome sequencing and
human genome mapping is giving researchers a much better idea of the ‘parts list’ for particular cells,” says Chesnut. “As well as simply sequencing protein-coding genes, we’re beginning to under- stand the role of the non-coding genome and piec- ing together the profile of mutations associated with particular disease states.”
Drug Discovery World Spring 2018
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