In vivo genome editing using nuclease-encoding mRNA corrects SP-B deficiency

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Figure 1: nec-mRNA cleaves the SP-B cassette, induces HDR in vitro and is expressed in lung cells in vivo.
Figure 2: Rescue of SP-B deficient mice by in vivo gene manipulation.


  1. 1

    Karikó, K. et al. Mol. Ther. 16, 1833–1840 (2008).

  2. 2

    Karikó, K., Muramatsu, H., Ludwig, J. & Weissman, D. Nucleic Acids Res. 39, e142 (2011).

  3. 3

    Kormann, M.S. et al. Nat. Biotechnol. 29, 154–157 (2011).

  4. 4

    Mays, L.E. et al. J. Clin. Invest. 123, 1216–1228 (2013).

  5. 5

    Karikó, K., Muramatsu, H., Keller, J.M. & Weissman, D. Mol. Ther. 20, 948–953 (2012).

  6. 6

    Melton, K.R. et al. Am. J. Physiol. Lung Cell. Mol. Physiol. 285, L543–L549 (2003).

  7. 7

    Schultze, N., Burki, Y., Lang, Y., Certa, U. & Bluethmann, H. Nat. Biotechnol. 14, 499–503 (1996).

  8. 8

    Nogee, L.M. Annu. Rev. Physiol. 66, 601–623 (2004).

  9. 9

    Clark, J.C. et al. Proc. Natl. Acad. Sci. USA 92, 7794–7798 (1995).

  10. 10

    Wang, Y. et al. Mol. Ther. 21, 358–367 (2013).

  11. 11

    Kumar, M.N. et al. J. Nanosci. Nanotechnol. 4, 990–994 (2004).

  12. 12

    Nafee, N., Taetz, S., Schneider, M., Schaefer, U.F. & Lehr, C.M. Nanomedicine 3, 173–183 (2007).

  13. 13

    Urnov, F.D. et al. Nature Biotechnology 435, 646–651 (2005).

  14. 14

    Doyon, Y. et al. Nat. Biotechnol. 26, 702–708 (2008).

  15. 15

    Ravi Kumar, M.N., Bakowsky, U. & Lehr, C.M. Biomaterials 25, 1771–1777 (2004).

  16. 16

    Held, H.D., Martin, C. & Uhlig, S. Br. J. Pharmacol. 126, 1191–1199 (1999).

  17. 17

    Pfaffl, M.W., Horgan, G.W. & Dempfle, L. Nucleic Acids Res. 30, e36 (2002).

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This work was supported by the Deutsche Forschungsgemeinschaft (DFG KO 4258/2-1, to M.S.D.K and L.E.M.), fortüne grant (no. 1980-0-0, to M.S.D.K.), by the European Respiratory Society (Maurizio Vignola Award, to M.S.D.K.), in part by the Mukoviszidose e.V. (S03/12 to M.S.D.K.), in part by the Deutsche Forschungsgemeinschaft Emmy Noether Programme (HA 5274/3-1, to D. H.), in part by the Interfaculty Center for Pharmacogenomics and Drug Research (ICEPHA Twinning Grant 22-0-0 to S.B.-H.) and in part by DFG (to B.N., S.B.-H. and M.G. (970/8.1)). Site-specific nucleases were kindly provided by Sangamo BioSciences. Thank you to D. Fraude for excellent illustration support. Primary antibody against SP-B was kindly provided by M.G.

Author information

M.S.D.K. designed research, and together with A.J.M. and A.D., carried out experiments and analyzed data. B.M. performed the isolated lung experiments, and together with S.B.-H., participated in the interpretation and analysis of the data, with S.B.-H. and B.N. providing administrative and technical support. M.A., E.M., B.L., L.E.M., J.R., D.M.B., P.R., P.S., F.Z., A.S., M.C. and M.B. conceived and performed experiments. M.G., M.S., R.H., D.H. and C.-M.L. provided materials. M.S.D.K. and L.E.M. wrote the manuscript. All authors discussed results and implications, commented on or edited parts of the manuscript.

Correspondence to Claus-Michael Lehr or Michael S D Kormann.

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Competing interests

M.S.D.K. and L.E.M. are listed as co-inventors on a patent application related to this work. M.S.D.K. is an inventor on a patent licensed to the biopharmaceutical company Ethris GmbH.

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Mahiny, A., Dewerth, A., Mays, L. et al. In vivo genome editing using nuclease-encoding mRNA corrects SP-B deficiency. Nat Biotechnol 33, 584–586 (2015).

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