RT Book, Section A1 Gerson, Stanton L. A2 Kaushansky, Kenneth A2 Prchal, Josef T. A2 Burns, Linda J. A2 Lichtman, Marshall A. A2 Levi, Marcel A2 Linch, David C. SR Print(0) ID 1178737988 T1 Gene Therapy for Hematologic Diseases T2 Williams Hematology, 10e YR 2021 FD 2021 PB McGraw-Hill Education PP New York, NY SN 9781260464122 LK hemonc.mhmedical.com/content.aspx?aid=1178737988 RD 2024/03/28 AB SUMMARYIn the past 5 years, gene therapy as a promise for hematologic diseases has become a reality. In fact, the term has expanded from providing genetic material to treat disease to incorporating a normal gene or cDNA to replace a defective or nonfunctional gene, or CRISPR (clustered regularly interspaced short palindromic repeats) genetic engineering to correct a point mutation. This has been a revolutionary period in a field first imagined in the 1980s. Treatment resulting from expression of a transferred gene (or transgene) in diseased or other cells by engineered vectors has now become approved by the U.S. Food and Drug Administration (FDA), and many other treatments are in development. When within the cell, and most often incorporated into DNA, the transgene can direct synthesis of a therapeutic protein that can complement a genetic deficiency or confer upon the cell a desired phenotype or function. Many clinical trials have involved gene therapy for patients with various gene-deficient or genetically mutational hematologic diseases, such as severe combined immunodeficiency, hemophilia, sickle cell disease, thalassemia, Wiskott-Aldrich syndrome, chronic granulomatous disease, congenital neutropenia, and HIV infection. Early results from these clinical trials indicate that gene therapy can cure or improve many inherited or acquired hematologic disorders. Recently, initial FDA and European approvals have been forthcoming. This chapter reviews the basic principles of gene transfer and the results of selected preclinical and clinical studies.