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GENE EDITING

Towards safe therapy for immunodeficiency

Nature Biomedical Engineering volume 1, pages 937–938 (2017)Cite this article

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A humanized mouse model of X-linked severe combined immunodeficiency suggests that the safety of correcting the human IL2RG gene in haematopoietic stem cells depends on both gene-correction frequency and the conditioning regimen used before cell transplantation.

Targeted gene-editing technologies for therapeutics aim to precisely modify the genome of living cells to provide substantial and enduring clinical benefit. Genome editing is enabled by engineered nucleases such as meganucleases, zinc finger nucleases1 (ZFNs), transcription activator-like effector nucleases2 and CRISPR–Cas nucleases3. These nucleases can be programmed to introduce targeted DNA double-strand breaks (DSBs), which in human cells are typically repaired by one of two competing DNA repair pathways: the error-prone non-homologous end-joining pathway (NHEJ), which often results in variable-length insertions or deletions (indels) useful for gene disruption, or the precise homology-directed repair (HDR) pathway, which can be co-opted for gene correction. Because NHEJ is the dominant repair pathway, with most genome-editing nucleases it is easier to achieve high-frequency disruption than correction.

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References

  1. Urnov, F. D., Rebar, M. C., Holmes, M. C., Zhang, S. & Gregory, P. D. Nat. Rev. Genet.11, 636–646 (2010).

    Article  CAS  Google Scholar 

  2. Joung, J. K. & Sander, J. D. Nat. Rev. Mol. Cell Biol.14, 49–55 (2012).

    Article  Google Scholar 

  3. Sander, J. D. & Joung, J. K. Nat. Biotechnol.32, 347–355 (2014).

    Article  CAS  Google Scholar 

  4. Schiroli, J. et al. Sci. Transl. Med.9, eaan0820 (2017).

    Article  Google Scholar 

  5. Tsai, S. Q. et al. Nat. Biotechnol.33, 187–197 (2015).

    Article  CAS  Google Scholar 

  6. Martins, V. C. et al. Nature509, 465–470 (2014).

    Article  CAS  Google Scholar 

  7. Cavazzana, M., Six, E., Lagresle-Peyrou, C., André-Schmutz, S. & Hacein-Bey-Abina, S. Hum. Gene Ther.27, 108–116 (2016).

    Article  CAS  Google Scholar 

  8. Hacein-Bey-Abina, S. et al. Science302, 415–419 (2003).

    Article  CAS  Google Scholar 

  9. Aiuti, A. N. Engl. J. Med.360, 447–458 (2009).

    Article  CAS  Google Scholar 

  10. Aiuti, A. Science296, 2410–2413 (2002).

    Article  CAS  Google Scholar 

  11. Shaw, K. L. & Kohn, D. B. Sci. Transl. Med.3, 97ps36 (2011).

    Article  Google Scholar 

  12. De Ravin, S. S. et al. Sci. Transl. Med.8, 335ra57 (2016).

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Hematology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Shengdar Q. Tsai

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  1. Shengdar Q. Tsai
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Correspondence to Shengdar Q. Tsai.

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Tsai, S.Q. Towards safe therapy for immunodeficiency. Nat Biomed Eng 1, 937–938 (2017). https://doi.org/10.1038/s41551-017-0174-x

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