@article{discovery1481142, pages = {317--327}, journal = {Trends In Molecular Medicine}, month = {April}, publisher = {ELSEVIER SCI LTD}, note = {Copyright {\copyright} 2016. This manuscript version is published under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International licence (CC BY-NC-ND 4.0). This licence allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licences are available at http://creativecommons.org/licenses/by/4.0. Access may be initially restricted by the publisher.}, title = {Treating Immunodeficiency through HSC Gene Therapy}, number = {4}, volume = {22}, year = {2016}, keywords = {Science \& Technology, Life Sciences \& Biomedicine, Biochemistry \& Molecular Biology, Cell Biology, Medicine, Research \& Experimental, Research \& Experimental Medicine, Chronic Granulomatous-disease, Leukocyte Adhesion Deficiency, Hematopoietic Stem-cells, Adenosine-deaminase-deficiency, Wiskott-aldrich Syndrome, Lentiviral Vector, Lymphoproliferative Disease, Murine Model, X-cgd, Mice}, issn = {1471-4914}, url = {http://dx.doi.org/10.1016/j.molmed.2016.02.002}, author = {Booth, C and Gaspar, HB and Thrasher, AJ}, abstract = {Haematopoietic stem cell (HSC) gene therapy has been successfully employed as a therapeutic option to treat specific inherited immune deficiencies, including severe combined immune deficiencies (SCID) over the past two decades. Initial clinical trials using first-generation gamma-retroviral vectors to transfer corrective DNA demonstrated clinical benefit for patients, but were associated with leukemogenesis in a number of cases. Safer vectors have since been developed, affording comparable efficacy with an improved biosafety profile. These vectors are now in Phase I/II clinical trials for a number of immune disorders with more preclinical studies underway. Targeted gene editing allowing precise DNA correction via platforms such as ZFNs, TALENs and CRISPR/Cas9 may now offer promising strategies to improve the safety and efficacy of gene therapy in the future.} }