Adenovirus vectors in hematopoietic stem cell genome editing. Issue 24 (20th November 2019)

• Record Type: Journal Article
• Authors: Li, Chang; Lieber, André
• Is Part Of: FEBS letters. Volume 593:Issue 24(2019)
• Page Start: 3623
• Page End: 3648
• Publication Date: 2019-11-20
• Subjects: adenovirus vector -- base editors -- CRISPR/Cas9 -- genome editing -- HSCs -- in vivo transduction -- targeted integration; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13668
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Genome editing of hematopoietic stem cells (HSCs) represents a therapeutic option for a number of hematological genetic diseases, as HSCs have the potential for self‐renewal and differentiation into all blood cell lineages. This review presents advances of genome editing in HSCs utilizing adenovirus vectors as delivery vehicles. We focus on capsid‐modified, helper‐dependent adenovirus vectors that are devoid of all viral genes and therefore exhibit an improved safety profile. We discuss HSC genome engineering for several inherited disorders and infectious diseases including hemoglobinopathies, Fanconi anemia, hemophilia, and HIV‐1 infection by ex vivo and in vivo editing in transgenic mice, nonhuman primates, as well as in human CD34 + cells. Mechanisms of therapeutic gene transfer including episomal expression of designer nucleases and base editors, transposase‐mediated random integration, and targeted homology‐directed repair triggered integration into selected genomic safe harbor loci are also reviewed. Abstract :