Pavlovic, KristinaTristán-Manzano, MaríaMaldonado-Pérez, NoeliaCortijo-Gutierrez, MarinaSánchez-Hernández, SabinaJusticia-Lirio, PedroCarmona, M. DoloresHerrera, ConchaMartin, FranciscoBenabdellah, Karim2022-07-062022-07-062020-09-29Pavlovic 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;11:570672http://hdl.handle.net/10668/3745Genome 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/ImmunotherapyCARsGene editingGraft-vs-host diseaseBase editorsInmunoterapiaReceptores quiméricos de antígenosEdición génicaEnfermedad injerto contra huéspedSistema inmunológicoMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::CRISPR-Associated ProteinsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, Genetic::Gene Silencing::CRISPR-Cas SystemsMedical Subject Headings::Chemicals and Drugs::Complex Mixtures::Biological Products::Vaccines::Cancer VaccinesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Engineering::Genetic TherapyMedical Subject Headings::Phenomena and Processes::Immune System Phenomena::Immune System Processes::Transplantation Immunology::Host vs Graft Reaction::Graft RejectionMedical Subject Headings::Diseases::Immune System Diseases::Graft vs Host DiseaseMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, AdoptiveMedical Subject Headings::Diseases::NeoplasmsZinc Finger Nucleasesreview article33117361open access10.3389/fimmu.2020.5706721664-3224PMC7553077