Nektarios Tavernarakis

Abstract:

In recent years, we are witnessing an explosion of technologies that allow DNA editing in various model organisms, even humans. Such technologies include meganucleases, zinc finger nucleases (ZFNs), transcription activator like effector nucleases (TALENs) and more recently the bacterial CRISPR/CAS system, which has been adopted for use in eukaryotes. The advent of genome editing technologies has revolutionized genetics in organisms ranging from invertebrates to mammals and enabled genetic manipulations not previously possible, massively accelerating the pace of research and discovery. The CRISPR/CAS system is the latest addition in the arsenal of such tools and even holds promise for allowing the modification of the human genome in a reliable manner. Initially studied in bacteria, the CRISPR/CAS system is at the core of a sophisticated prokaryotic immune response, protecting bacterial cells against phage infection. After its initial successful implementation in eukaryotic cells, the CRISPR/CAS system has proven remarkably versatile and efficient with diverse applications in numerous organisms, including human cells. The system not only allows the introduction of specific alterations to the genome, such as insertions, deletions, single base pair changes, gene knock-outs and replacements, etc., but also gene activation and silencing, chromosome and locus labeling, chromatin remodeling and others. The already demonstrated potential of CRISPR/CAS brings closer the prospect of directed molecular interventions towards restoring genetic lesions associated with human pathology. The development of precision medicine approaches, involving the generation of personalized animal models of human diseases, as well as ex vivo cell therapies, organoid-based drug screening, and genome engineering are now entering the realm of feasibility. Given the disruptive potential of genome editing technologies relevant to medicine, biotechnology and basic research it is important to carefully consider caveats and limitations. We will discuss emergent developments and applications of genome editing technologies, as well as, considerations arising at the current state of the art.