The use of precise, rationally designed gene-editing nucleases allows for targeted genome and transcriptome modification, and at present, four major classes of nucleases are being employed: zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), meganucleases (MNs), and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9. Each reagent shares the ability to recognize and bind a target sequence of DNA. Depending on the properties of the reagent, the DNA can be cleaved on one or both strands, or epigenetic changes can be mediated. These novel properties can impact hematological disease by allowing for: (1) direct modification of hematopoietic stem/progenitor cells (HSPCs), (2) gene alteration of hematopoietic lineage committed terminal effectors, (3) genome engineering in non-hematopoietic cells with reprogramming to a hematopoietic phenotype, and (4) transcriptome modulation for gene regulation, modeling, and discovery.
Bibliographical noteFunding Information:
MJO and JT appreciate funding support from The Children's Cancer Research Fund, the Epidermolysis Bullosa Research Partnership, Epidermolysis Bullosa Medical Research Fund, Sohana Research Fund, Richard M Schulze Family Foundation, DebRA, the Lindahl Family, and the Corrigan Family. JT is supported in part by R01 AR063070, R01 AR059947, DOD W81XWH-12-1-0609, and P01 CA065493. MJO is supported by 8UL1TR000114-02. JB is supported by a grant from the National Science Foundation to DV (IOS-1339209). Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114 (MJO). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
- Blood disorders
- Hematopoietic stem cells