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. 2021 Feb 1;10(3):513. doi: 10.3390/jcm10030513

Figure 1.

Figure 1

Gene therapy approaches for inherited blood disorders. (a) General scheme for gene therapies of inherited blood disorders: (1) Isolation of CD34+ hematopoietic stem and progenitor cells (HSPCs) from bone marrow harvests or mobilized peripheral blood cell collections; (2) Ex vivo genetic modification of HSPCs; (3) Adoptive transfer of genetically corrected cells to the patient generally following a reduced intensity conditioning regimen to enhance engraftment of the treated cells. (b) Largely random pattern of transgene integration within the target cellular genome after genetic modification of HSPCs using integrating viral vectors based on lentiviruses or gamma-retroviruses. (c) Precise integration of therapeutic genes using genome editing approaches based on zinc-finger nucleases (ZFNs), transcription activator-like effector (TALE) nucleases (TALENS), or the clustered regularly interspaced palindrome repeat (CRISPR)-associated (Cas) platform. Abbreviations: crRNA, CRISPR RNA; dsDNA, double-stranded DNA; DSBs, double-stranded breaks; HDR, homology directed repair; NHEJ, non-homologous end-joining; PAM, protospacer-adjacent motif; sgRNA, single guide RNA; ssRNA, single-stranded RNA; tracrRNA, trans-activating CRISPR RNA.