With an approval likely at the EMA, ex vivo gene therapy in hematopoietic stem cells appears poised for prime time.
Your institute does not have access to this article
Open Access articles citing this article.
Orphanet Journal of Rare Diseases Open Access 20 July 2018
Subscribe to Journal
Get full journal access for 1 year
only $8.25 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Qasim, W., Gaspar, H.B. & Thrasher, A.J. Update on clinical gene therapy in childhood. Arch. Dis. Child. 92, 1028–1031 (2007).
Williams, D.A. & Thrasher, A.J. Concise review: lessons learned from clinical trials of gene therapy in monogenic immunodeficiency diseases. Stem Cells Transl. Med. 3, 636–642 (2014).
Cavazzana-Calvo, M. et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 288, 669–672 (2000).
Hacein-Bey-Abina, S. et al. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N. Engl. J. Med. 348, 255–256 (2003).
Braun, C.J. et al. Gene therapy for Wiskott-Aldrich syndrome—long-term efficacy and genotoxicity. Sci. Transl. Med. 6, 227ra33 (2014).
Cavazzana-Calvo, M. et al. Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia. Nature 467, 318–322 (2010).
Biffi, A. et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 341, 1233158 (2013).
Cartier, N. et al. Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science 326, 818–823 (2009).
bluebird bio presents oncology and gene therapy data at the ASGCT 19th Annual Meeting. http://investor.bluebirdbio.com/phoenix.zhtml?c=251820&p=irol-newsArticle&ID=2166363 (9 May 2016).
Hütter, G. et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N. Engl. J. Med. 360, 692–698 (2009).
Perez, E.E. et al. Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat. Biotechnol. 26, 808–816 (2008).
Burke, B.P. et al. Engineering cellular resistance to HIV-1 infection in vivo using a dual therapeutic lentiviral vector. Mol. Ther. Nucleic Acids 4, e236 (2015).
Xu, J. et al. Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A. Proc. Natl. Acad. Sci. USA 110, 6518–6523 (2013).
Bauer, D.E. et al. An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Science 342, 253–257 (2013).
Wang, J. et al. Homology-driven genome editing in hematopoietic stem and progenitor cells using ZFN mRNA and AAV6 donors. Nat. Biotechnol. 33, 1256–1263 (2015).
Sather, B.D. et al. Efficient modification of CCR5 in primary human hematopoietic cells using a megaTAL nuclease and AAV donor template. Sci. Transl. Med. 7, 307ra156 (2015).
De Ravin, S.S. et al. Targeted gene addition in human CD34(+) hematopoietic cells for correction of X-linked chronic granulomatous disease. Nat. Biotechnol. 34, 424–429 (2016).
Kaufmann, K.B., Büning, H., Galy, A., Schambach, A. & Grez, M. Gene therapy on the move. EMBO Mol. Med. 5, 1642–1661 (2013).
Shaw, K.L. & Kohn, D.B. A tale of two SCIDs. Sci. Transl. Med. 3, 97ps36 (2011).
Aiuti, A. et al. Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science 296, 2410–2413 (2002).
Aiuti, A. et al. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N. Engl. J. Med. 360, 447–458 (2009).
Gaspar, H.B. et al. Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning. Mol. Ther. 14, 505–513 (2006).
Gaspar, H.B. et al. Hematopoietic stem cell gene therapy for adenosine deaminase-deficient severe combined immunodeficiency leads to long-term immunological recovery and metabolic correction. Sci. Transl. Med. 3, 97ra80 (2011).
Candotti, F. et al. Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans. Blood 120, 3635–3646 (2012).
Hacein-Bey-Abina, S. et al. A modified γ-retrovirus vector for X-linked severe combined immunodeficiency. N. Engl. J. Med. 371, 1407–1417 (2014).
Hacein-Bey Abina, S. et al. Outcomes following gene therapy in patients with severe Wiskott-Aldrich syndrome. J. Am. Med. Assoc. 313, 1550–1563 (2015).
Aiuti, A. et al. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science 341, 1233151 (2013).
Hoban, M.D. et al. Correction of the sickle cell disease mutation in human hematopoietic stem/progenitor cells. Blood 125, 2597–2604 (2015).
Tebas, P. et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N. Engl. J. Med. 370, 901–910 (2014).
Peterson, C.W. et al. Multilineage polyclonal engraftment of Cal-1 gene-modified cells and in vivo selection after SHIV infection in a nonhuman primate model of AIDS. Mol. Ther. Methods Clin. Dev. 3, 16007 (2016).
Mukherjee, S. & Thrasher, A.J. Gene therapy for PIDs: progress, pitfalls and prospects. Gene 525, 174–181 (2013).
Cesana, D. et al. Uncovering and dissecting the genotoxicity of self-inactivating lentiviral vectors in vivo. Mol. Ther. 22, 774–785 (2014).
About this article
Cite this article
Scott, C., DeFrancesco, L. Gene therapy's out-of-body experience. Nat Biotechnol 34, 600–607 (2016). https://doi.org/10.1038/nbt.3592
Orphanet Journal of Rare Diseases (2018)