Abstract
Genome editing technologies, particularly CRISPR-Cas (clustered regularly interspaced short palindromic repeats (CRISPR) associated nucleases), are redefining the boundaries of therapeutic gene therapy. CRISPR-Cas is a robust, straightforward, and programmable genome editing tool capable of mediating site-specific DNA modifications. The rapid advancements from discovery to clinical adaptation have expanded the therapeutic landscape to treat genetically defined diseases. Together with the technical developments in human DNA and RNA sequencing, CRISPR-directed gene therapy enables a new era to realize precision medicine where pathogenic mutations underlying monogenic disorders can potentially be corrected. Also, protective or therapeutic genomic alterations can be introduced as preventative or curative therapy. Despite its high therapeutic potential, CRISPR-CasĀ“ clinical translation is still in its infancy and is highly dependent on its efficiency, specificity in gene corrections, and cell-specific delivery. Therefore, this chapter focuses on the challenges and opportunities the CRISPR-Cas toolbox offers together with delivery vehicles to realize its use for therapeutic gene editing. Furthermore, we discuss the obstacles the CRISPR-Cas system faces for successful clinical translation and summarize its current clinical progress.
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Acknowledgments
This work was supported by the Project EVICARE (No. 725229) of the European Research Council (ERC) to J.P.G.S, co-funded by the Project SMARTCARE-II of the BioMedicalMaterials institute to JPGS, the ZonMw-TAS program (No. 116002016) to J.P.G.S./Z.L., PPS grant (No. 2018B014) to J.P.G.S./P.V/Z.L, the Dutch Ministry of Economic Affairs, Agriculture and Innovation and the Netherlands CardioVascular Research Initiative (CVON): the Dutch Heart Foundation to J.P.G.S, Dutch Federations of University Medical Centers, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences. We thank Marieke Roefs for her comments and suggestions to improve this review. The figures were created with BioRender.com.
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Ilahibaks, N.F., Hulsbos, M.J., Lei, Z., Vader, P., Sluijter, J.P.G. (2023). Enabling Precision Medicine with CRISPR-Cas Genome Editing Technology: A Translational Perspective. In: Xiao, J. (eds) Genome Editing in Cardiovascular and Metabolic Diseases. Advances in Experimental Medicine and Biology, vol 1396. Springer, Singapore. https://doi.org/10.1007/978-981-19-5642-3_20
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