RT Journal Article T1 Using Gene Editing Approaches to Fine-Tune the Immune System A1 Pavlovic, Kristina A1 Tristán-Manzano, María A1 Maldonado-Pérez, Noelia A1 Cortijo-Gutierrez, Marina A1 Sánchez-Hernández, Sabina A1 Justicia-Lirio, Pedro A1 Carmona, M. Dolores A1 Herrera, Concha A1 Martin, Francisco A1 Benabdellah, Karim K1 Immunotherapy K1 CARs K1 Gene editing K1 Graft-vs-host disease K1 Base editors K1 Inmunoterapia K1 Receptores quiméricos de antígenos K1 Edición génica K1 Enfermedad injerto contra huésped K1 Sistema inmunológico AB Genome editing technologies not only provide unprecedented opportunities to study basic cellular system functionality but also improve the outcomes of several clinical applications. In this review, we analyze various gene editing techniques used to fine-tune immune systems from a basic research and clinical perspective. We discuss recent advances in the development of programmable nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas-associated nucleases. We also discuss the use of programmable nucleases and their derivative reagents such as base editing tools to engineer immune cells via gene disruption, insertion, and rewriting of T cells and other immune components, such natural killers (NKs) and hematopoietic stem and progenitor cells (HSPCs). In addition, with regard to chimeric antigen receptors (CARs), we describe how different gene editing tools enable healthy donor cells to be used in CAR T therapy instead of autologous cells without risking graft-versus-host disease or rejection, leading to reduced adoptive cell therapy costs and instant treatment availability for patients. We pay particular attention to the delivery of therapeutic transgenes, such as CARs, to endogenous loci which prevents collateral damage and increases therapeutic effectiveness. Finally, we review creative innovations, including immune system repurposing, that facilitate safe and efficient genome surgery within the framework of clinical cancer immunotherapies. PB Frontiers YR 2020 FD 2020-09-29 LK http://hdl.handle.net/10668/3745 UL http://hdl.handle.net/10668/3745 LA en NO Pavlovic K, Tristán-Manzano M, Maldonado-Pérez N, Cortijo-Gutierrez M, Sánchez-Hernández S, Justicia-Lirio P, et al. Using Gene Editing Approaches to Fine-Tune the Immune System. Front Immunol. 2020 Sep 29;11:570672 DS RISalud RD Apr 5, 2025