Rational design of cationic lipids for siRNA delivery (original) (raw)
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Acknowledgements
The authors thank K. McClintock for assistance with animal studies. The authors also thank the Centre for Drug Research and Development at the University of British Columbia for use of the NMR facilities and M. Heller for his expert assistance in setting up the 31P-NMR experiments.
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- Jianxin Chen, Barbara L Mui, Ying K Tam, Thomas D Madden & Michael J Hope
Present address: Present address: Alcana Technologies, Vancouver, British Columbia, Canada., - Sean C Semple and Akin Akinc: These authors contributed equally to this work.
Authors and Affiliations
- Tekmira Pharmaceuticals, Burnaby, British Columbia, Canada
Sean C Semple, Jianxin Chen, Ammen P Sandhu, Barbara L Mui, Connie K Cho, Derrick Stebbing, Erin J Crosley, Ed Yaworski, Kieu Lam, Lloyd B Jeffs, Merete L Eisenhardt, Sandra K Klimuk, Ying K Tam, Ian MacLachlan, Thomas D Madden & Michael J Hope - Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA
Akin Akinc, Dinah W Y Sah, J Robert Dorkin, June Qin, Kallanthottathil G Rajeev, Lubomir Nechev, Muthusamy Jayaraman, Martin A Maier, Michael J Weinstein, Qingmin Chen, Rene Alvarez, Scott A Barros, Soma De, Todd Borland, Verbena Kosovrasti, William L Cantley, Muthiah Manoharan, Mark A Tracy & Antonin de Fougerolles - Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada
Ismail M Hafez, Kim F Wong, Mikameh Kazem & Pieter R Cullis - Department of Chemistry, University of British Columbia, Vancouver, British Columbia, Canada
Masuna Srinivasulu & Marco A Ciufolini
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Contributions
J.C., M.A.C., P.R.C., T.D.M., M.J.H. and K.F.W. designed and advised on novel lipids. J.C., K.F.W. and M.S. synthesized novel lipids. M.J.H., T.D.M., J.C., K.F.W., M.M., K.G.R., M.A.M., M.T. and M.J. analyzed and interpreted lipid data. T.D.M., M.J.H. and M.A.T. co-directed novel lipid synthesis and screening program. S.C.S. designed and directed rodent in vivo studies. S.C.S., S.K.K., B.L.M., K.L., M.L.E., M.K., A.P.S., Y.K.T., S.A.B., W.L.C., M.J.W. and E.J.C. generated rodent in vivo data, including Factor VII and tolerability analyses. L.N., V.K., T.B., R.A., Q.C. and D.W.Y.S. developed novel siRNAs targeting TTR. R.A. and A.A. designed and directed NHP in vivo studies. S.C.S., S.K.K., A.A., B.L.M., I.M., A.P.S., Y.K.T., R.A., T.B., D.W. Y. S., S.A.B., J.Q., J.R.D. and A.d.F. analyzed and interpreted in vivo data. B.L.M., K.L., A.P.S., S.K.K., S.C.S. and E.J.C. generated and characterized preformed vesicle formulations with novel lipids. D.S. and C.K.C. developed methods and designed and conducted HPLC lipid analyses of preformed vesicle formulations. E.Y. and L.B.J. prepared SNALP formulations. P.R.C. directed biophysical studies and advised on methods. A.P.S., I.M.H., S.D. and K.W. performed biophysical characterization studies (p_K_a, NMR, differential scanning calorimetric) of novel lipids and formulations. M.J.H., P.R.C., T.D.M., A.P.S., I.M.H. and K.F.W. analyzed biophysical data. S.C.S., M.J.H., A.A. and P.R.C. co-wrote the manuscript. T.D.M., M.M., M.A.M., M.A.T. and A.D.F. reviewed and edited the manuscript. S.C.S., M.J.H., A.A., P.R.C., I.M. and A.D.F. were responsible for approval of the final draft.
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Correspondence toSean C Semple or Akin Akinc.
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Authors are employees of Alnylam, Tekmira, or Alcana or receive funding from Alnylam.
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Semple, S., Akinc, A., Chen, J. et al. Rational design of cationic lipids for siRNA delivery.Nat Biotechnol 28, 172–176 (2010). https://doi.org/10.1038/nbt.1602
- Received: 16 September 2009
- Accepted: 17 December 2009
- Published: 17 January 2010
- Issue Date: February 2010
- DOI: https://doi.org/10.1038/nbt.1602