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Assessing unintended hybridization-induced biological effects of oligonucleotides

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Figure 1: Assessment of hybridization-based off-target effects starts with a mechanism- and chemistry-dependent in silico screen, which is interpreted and validated on a case-by-case basis using auxiliary information and experiments.


  1. Zamecnik, P.C. & Stephenson, M.L. Proc. Natl. Acad. Sci. USA 75, 280–284 (1978).

    Article  CAS  Google Scholar 

  2. Fire, A. et al. Nature 391, 806–811 (1998).

    Article  CAS  Google Scholar 

  3. Henry, S. et al. Toxicologic properties of 2′-methoxyethyl chimeric antisense inhibitors in animals and man. in Antisense Drug Technology: Principles Strategies, and Applications. (ed. Crooke, S.T.) 327–364 (CRC Press, 2007).

    Google Scholar 

  4. Sheehan, J.P. & Phan, T.M. Biochemistry 40, 4980–4989 (2001).

    Article  CAS  Google Scholar 

  5. Bennett, C.F. & Swayze, E.E. Annu. Rev. Pharmacol. Toxicol. 50, 259–293 (2010).

    Article  CAS  Google Scholar 

  6. Burchard, J. et al. RNA 15, 308–315 (2009).

    Article  CAS  Google Scholar 

  7. Jackson, A.L. et al. RNA 12, 1179–1187 (2006).

    Article  CAS  Google Scholar 

  8. Snøve, O. & Holen, T. Biochem. Biophys. Res. Commun. 319, 256–263 (2004).

    Article  Google Scholar 

  9. Jackson, A.L. et al. Nat. Biotechnol. 21, 635–637 (2003).

    Article  CAS  Google Scholar 

  10. Schwarz, D.S. et al. PLoS Genet. 2, e140 (2006).

    Article  Google Scholar 

  11. Obad, S. et al. Nat. Genet. 43, 371–378 (2011).

    Article  CAS  Google Scholar 

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Correspondence to Arthur A Levin.

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The authors are employees in, or consultants for, commercial companies actively developing oligonucleotides as drugs. See affiliation section for details.

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Lindow, M., Vornlocher, HP., Riley, D. et al. Assessing unintended hybridization-induced biological effects of oligonucleotides. Nat Biotechnol 30, 920–923 (2012).

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