Gene therapy of hematological disorders: current challenges

• Published in: Gene therapy Vol. 26; no. 7-8; pp. 296 - 307
• Main Author: Al-Saif, Amr M
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.08.2019
• Subjects: Animals; Autografts; Blood diseases; Care and treatment; Clinical trials; Gene Editing - methods; Gene therapy; Gene Transfer Techniques; Genetic engineering; Genetic Therapy - adverse effects; Genetic Therapy - methods; Genome editing; Genomes; Hematologic Diseases - therapy; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Humans; Primary immunodeficiencies; Stem cell transplantation; Stem cells; Transplantation
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/s41434-019-0093-4

Recent advances in genetic engineering technology and stem cell biology have spurred great interest in developing gene therapies for hereditary, as well as acquired hematological disorders. Currently, hematopoietic stem cell transplantation is used to cure disorders such as hemoglobinopathies and primary immunodeficiencies; however, this method is limited by the availability of immune-matched donors. Using autologous cells coupled with genome editing bypasses this limitation and therefore became the focus of many research groups aiming to develop efficient and safe genomic modification. Hence, gene therapy research has witnessed a noticeable growth in recent years with numerous successful achievements; however, several challenges have to be overcome before gene therapy becomes widely available for patients. In this review, I discuss tools used in gene therapy for hematological disorders, choices of target cells, and delivery vehicles with emphasis on current hurdles and attempts to solve them, and present examples of successful clinical trials to give a glimpse of current progress.