Gene Editing: Regulatory and Translation to Clinic

Hematol Oncol Clin North Am. 2017 Oct;31(5):797-808. doi: 10.1016/j.hoc.2017.06.002.

Abstract

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.

Keywords: CCR5; Genome editing; Genotoxicity; Hematopoietic stem and progenitor cells; Safety assessment; Zinc finger nucleases.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic
  • Endonucleases / chemistry
  • Endonucleases / metabolism
  • Gene Editing* / legislation & jurisprudence
  • Gene Editing* / methods
  • Gene Knockout Techniques
  • Genetic Therapy / adverse effects
  • Genetic Therapy / methods
  • Genetic Vectors / genetics
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Mutagenicity Tests
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • Receptors, CCR5 / chemistry
  • Receptors, CCR5 / metabolism
  • Risk Assessment
  • Translational Research, Biomedical* / legislation & jurisprudence
  • Translational Research, Biomedical* / methods
  • Zinc Fingers

Substances

  • RNA, Messenger
  • Receptors, CCR5
  • Endonucleases