The clinical application and regulatory strategy of genome editing for ex vivo cell therapy is derived from the intersection of two fields of study: viral vector gene therapy trials; and clinical trials with ex vivo purification and engraftment of CD34 + hematopoietic stem cells, T cells, and tumor cell vaccines. This article covers the regulatory and translational preclinical activities needed for a genome editing clinical trial modifying hematopoietic stem cells and the genesis of this current strategy based on previous clinical trials using genome-edited T cells. The SB-728 zinc finger nuclease platform is discussed because this is the most clinically advanced genome editing technology.
Key points
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This review covers the regulatory and translational preclinical activities needed for a CCR5 zinc finger nuclease genome editing clinical trial modifying hematopoietic stem cells.
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CD34 + HSPC manufacturing and clinical administration considerations are discussed.
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Preclinical evaluations supporting the FIH study include on- and off-target genome editing assessment, in vitro differentiation, in vivo stem cell engraftment, karyotype analysis, 53BP1 assay, soft agar transformation, and an NSG mouse tumorigenicity study.
Related posts:
In Vivo Hematopoietic Stem Cell Transduction
Therapeutic Gene Editing Safety and Specificity
Opening Marrow Niches in Patients Undergoing Autologous Hematopoietic Stem Cell Gene Therapy
Hematopoietic Gene Therapies for Metabolic and Neurologic Diseases
Gene Modified T Cell Therapies for Hematological Malignancies
Gene Therapy Approaches to Human Immunodeficiency Virus and Other Infectious Diseases
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