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The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs

The regulatory approval of Onpattro, a lipid nanoparticle-based short interfering RNA drug for the treatment of polyneuropathies induced by hereditary transthyretin amyloidosis, paves the way for clinical development of many nucleic acid-based therapies enabled by nanoparticle delivery.

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Fig. 1: Integrated model of lipid nanoparticle (LNP)-mediated delivery of siRNA to hepatocytes in vivo.
Fig. 2: LNP siRNA systems containing 2nd generation ionizable aminolipids exhibit greatly improved potency for silencing factor VII (FVII) in the liver.
Fig. 3: Phase I clinical trials of ALN-TTR01 and ALN-TTR02 (patisiran).


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Correspondence to Pieter R. Cullis.

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A.A., M.A.M., M.M., K.F., M.J. and S.B. are employees of Alnylam Pharmaceuticals. S.A., X.D., M.J.H., T.D.M., B.L.M., S.C.S. and Y.K.T. are employees of Acuitas. P.R.C. has financial holdings in Acuitas.

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Akinc, A., Maier, M.A., Manoharan, M. et al. The Onpattro story and the clinical translation of nanomedicines containing nucleic acid-based drugs. Nat. Nanotechnol. 14, 1084–1087 (2019).

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