Using Gene Editing Approaches to Fine-Tune the Immune System
Metadatos
Mostrar el registro completo del ítemAutor
Pavlovic, Kristina; Tristán Manzano, María; Maldonado Pérez, Noelia; Cortijo Gutierrez, Marina; Sánchez Hernández, Sabina; Justicia Lirio, Pedro; Martín Molina, Francisco; Benabdellah, KarimEditorial
Frontiers Media SA
Materia
Immunotherapy CARs Gene editing Graft-vs-host disease Base editors
Fecha
2020-09-29Referencia bibliográfica
Pavlovic K, Tristán-Manzano M, Maldonado-Pérez N, Cortijo-Gutierrez M, Sánchez-Hernández S, Justicia-Lirio P, Carmona MD, Herrera C, Martin F and Benabdellah K (2020) Using Gene Editing Approaches to Fine-Tune the Immune System. Front. Immunol. 11:570672. [doi: 10.3389/fimmu.2020.570672]
Patrocinador
Spanish ISCIII Health Research Fund; European Union (EU) PI12/01097 PI15/02015 PI18/00337 PI18/00330; CECEyU and CSyF councils of the Junta de Andalucia FEDER/European Cohesion Fund (FSE) 2016000073391-TRA 2016000073332-TRA PI-57069 PAIDI-Bio326 PI-0014-2016; Nicolas Monardes regional Ministry of Health 0006/2018; Spanish Government FPU16/05467 FPU17/02268; Industrial Doctorate Plan MCI DIN2018-010180; SMSI PEJ-2018-001760-A; LentiStem BiotechResumen
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 finetune
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.