| Autor: |
George CA; Innovative Genomics Institute, University of California Berkeley, Berkeley, California, USA.; Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, USA., Sahu SU; Innovative Genomics Institute, University of California Berkeley, Berkeley, California, USA.; Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, USA., de Oñate L; Innovative Genomics Institute, University of California Berkeley, Berkeley, California, USA.; Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, USA., Souza BSF; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador, Brazil.; Pioneer Science Initiative, D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil., Wilson RC; Innovative Genomics Institute, University of California Berkeley, Berkeley, California, USA.; Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, USA.; California Institute for Quantitative Biosciences, University of California Berkeley, Berkeley, California, USA. |
| Abstrakt: |
Hematopoietic stem cells (HSCs) provide the body with a continuous supply of healthy, functional blood cells. In patients with hematopoietic malignancies, immunodeficiencies, lysosomal storage disorders, and hemoglobinopathies, therapeutic genome editing offers hope for corrective intervention, with even modest editing efficiencies likely to provide clinical benefit. Engineered white blood cells, such as T cells, can be applied therapeutically to address monogenic disorders of the immune system, HIV infection, or cancer. The versatility of CRISPR-based tools allows countless new medical interventions for diseases of the blood, and rapid ex vivo success has been demonstrated in hemoglobinopathies via transplantation of the patient's HSCs following genome editing in a laboratory setting. Here we review recent advances in therapeutic genome editing of HSCs and T cells, focusing on the progress in ex vivo contexts, the promise of improved access via in vivo delivery, as well as the ongoing preclinical efforts that may enable the transition from ex vivo to in vivo administration. We discuss the challenges, limitations, and future prospects of this rapidly developing field, which may one day establish CRISPR as the standard of care for some diseases affecting the blood. |
