Page 469 - Williams Hematology ( PDFDrive )

444 Part V: Therapeutic Principles Chapter 29: Gene Therapy for Hematologic Diseases 445

Using ZFN, a DNA (up to 9.6 kb) can be inserted precisely into a 25. Zhang L, Thrasher AJ, Gaspar HB: Current progress on gene therapy for primary
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selected location of the human genome. There are several known “safe immunodeficiencies. Gene Ther 20(10):963–969, 2013.
harbors” in the human genome. For example, the PPP1R12C gene on 26. Aiuti A, Cattaneo F, Galimberti S, et al: Gene therapy for immunodeficiency due to
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chromosome 19 (AAVS1 locus) is frequently integrated by an AAV and 27. Candotti F, Shaw KL, Muul L, et al: Gene therapy for adenosine deaminase-deficient
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pathologic events. Several genes have been inserted into the AAVS1 28. Gaspar HB, Cooray S, Gilmour KC, et al: Hematopoietic stem cell gene therapy for
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site in human cells, including stem cells, using ZFN gene-targeting adenosine deaminase-deficient severe combined immunodeficiency leads to long-term
methods. 60,62 The gene correction rate of gene editing is still very low immunological recovery and metabolic correction. Sci Transl Med 3(97):97ra80, 2011.
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(approximately 1 percent). Fortunately, gene targeting is a fast-growing 29. Aiuti A, Bacchetta R, Seger R, et al: Gene therapy for primary immunodeficiencies:
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scription activator-like effector nuclease (TALEN) and the clustered, lymphocytes after family haploidentical haemopoietic stem-cell transplantation for
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