Premium
Adenovirus vectors in hematopoietic stem cell genome editing
Author(s) -
Li Chang,
Lieber André
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13668
Subject(s) - genome editing , biology , stem cell , genome engineering , haematopoiesis , genome , fanconi anemia , genetic enhancement , viral vector , transcription activator like effector nuclease , zinc finger nuclease , computational biology , hematopoietic stem cell , genetics , virology , gene , dna repair , recombinant dna
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.