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Development of Lipidoid–siRNA Formulations for Systemic Delivery to the Liver

Akinc, Akin, Goldberg, Michael, Qin, June, Dorkin, J Robert, Gamba-Vitalo, Christina, Maier, Martin, Jayaprakash, K Narayanannair, Jayaraman, Muthusamy, Rajeev, Kallanthottathil G, Manoharan, Muthiah, Koteliansky, Victor, Röhl, Ingo, Leshchiner, Elizaveta S, Langer, Robert, Anderson, Daniel G·2009·Molecular Therapy
DOI 10.1038/mt.2009.36
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Figure 1 The structures of 98N 12 -5(1), the five-tailed isomer of triethylenetetramine-laurylaminopropionate with a free internal amine, Cholesterol, and mPEG 2000 -C14 Glyceride.
Figure 1 The structures of 98N 12 -5(1), the five-tailed isomer of triethylenetetramine-laurylaminopropionate with a free internal amine, Cholesterol, and mPEG 2000 -C14 Glyceride.CC-BY-NC-ND · From the PDF
Figure 2 Maximization of siRNA loading into 98N 12 -5(1)-based formulation. ( a ) siRNA entrapment at various initial lipid:siRNA (wt:wt) ratios. ( b ) Removal of nonentrapped siRNA from a formulation with initial lipid:siRNA ratio of 5:1 using tangential flow filtration (TFF) (100,000 ­ molecular weight cutoff). Entrapment was measured before and after TFF with five volumes of buffer exchange. ( c,d ) C57BL/6 mice ( n = 3) received a single intravenous dose of 1.5, 2, or 10 mg/kg of Factor VII targeting siRNA formulated at different lipid:siRNA ratios. Control animals received saline ­ injections. ( c ) Weight gain 48 hours postadministration for 10 mg/kg groups shown. ( d ) Serum Factor VII protein levels measured 48 hours ­ postadministration. Data points represent group mean ± SD. PBS, phosphate-buffered saline; siRNA, small interfering RNA.
Figure 2 Maximization of siRNA loading into 98N 12 -5(1)-based formulation. ( a ) siRNA entrapment at various initial lipid:siRNA (wt:wt) ratios. ( b ) Removal of nonentrapped siRNA from a formulation with initial lipid:siRNA ratio of 5:1 using tangential flow filtration (TFF) (100,000 ­ molecular weight cutoff). Entrapment was measured before and after TFF with five volumes of buffer exchange. ( c,d ) C57BL/6 mice ( n = 3) received a single intravenous dose of 1.5, 2, or 10 mg/kg of Factor VII targeting siRNA formulated at different lipid:siRNA ratios. Control animals received saline ­ injections. ( c ) Weight gain 48 hours postadministration for 10 mg/kg groups shown. ( d ) Serum Factor VII protein levels measured 48 hours ­ postadministration. Data points represent group mean ± SD. PBS, phosphate-buffered saline; siRNA, small interfering RNA.CC-BY-NC-ND · From the PDF
Figure 3 Impact of PEG lipid alkyl chain length and particle size on in vivo activity. ( a,b ) C57BL/6 mice ( n = 3) received a single intravenous dose of either 2.5 or 20 mg/kg of Factor VII targeting siRNA formulated with PEG-lipids with different alkyl chain lengths (C10-C16). Control ­ animals received saline injections. ( a ) Weight gain and ( b ) serum Factor VII protein levels 48 hours postadministration shown. ( c ) C57BL/6 mice ( n = 3) received a single intravenous dose of 3 mg/kg of Factor VII targeting siRNA formulated in lipidoid nanoparticles with different mean particle sizes. Control animals received saline injections. Serum Factor VII protein levels were measured 48 hours postadministration. Data points represent group mean ± SD. PBS, phosphate-buffered saline; PEG, poly(ethylene glycol); siRNA, small interfering RNA.
Figure 3 Impact of PEG lipid alkyl chain length and particle size on in vivo activity. ( a,b ) C57BL/6 mice ( n = 3) received a single intravenous dose of either 2.5 or 20 mg/kg of Factor VII targeting siRNA formulated with PEG-lipids with different alkyl chain lengths (C10-C16). Control ­ animals received saline injections. ( a ) Weight gain and ( b ) serum Factor VII protein levels 48 hours postadministration shown. ( c ) C57BL/6 mice ( n = 3) received a single intravenous dose of 3 mg/kg of Factor VII targeting siRNA formulated in lipidoid nanoparticles with different mean particle sizes. Control animals received saline injections. Serum Factor VII protein levels were measured 48 hours postadministration. Data points represent group mean ± SD. PBS, phosphate-buffered saline; PEG, poly(ethylene glycol); siRNA, small interfering RNA.CC-BY-NC-ND · From the PDF
Figure 4 Key physical attributes of LNP01. ( a ) Volume-averaged particle size distribution by dynamic light scattering. Data shown as an overlay of three independent measurements. ( b ) Zeta potential measurement in 0.1× PBS. Data shown as an overlay of three independent measurements. ( c ) Serum stability of unformulated and LNP01-formulated siRNA. Samples were incubated in human serum at 37 °C for various times, and integrity of siRNA was measured using high-performance liquid chromatography. PBS, phosphate-buffered saline; siRNA, small interfering RNA.
Figure 4 Key physical attributes of LNP01. ( a ) Volume-averaged particle size distribution by dynamic light scattering. Data shown as an overlay of three independent measurements. ( b ) Zeta potential measurement in 0.1× PBS. Data shown as an overlay of three independent measurements. ( c ) Serum stability of unformulated and LNP01-formulated siRNA. Samples were incubated in human serum at 37 °C for various times, and integrity of siRNA was measured using high-performance liquid chromatography. PBS, phosphate-buffered saline; siRNA, small interfering RNA.CC-BY-NC-ND · From the PDF
Figure 5 Activity is maintained upon repeat administration of LNP01. C57BL/6 mice ( n = 5) received a bolus intravenous (IV) injection of either saline, LNP01-formulated control siRNA (siCont) at 5 mg/kg, or LNP01-formulated Factor VII targeting siRNA (siFVII) at 5 mg/kg. Serum samples were collected at various time points and Factor VII protein ­ levels were determined in the samples. After recovery of Factor VII levels to baseline values, animals were redosed on the indicated days. Data were collected for three treatment cycles. Data are displayed as relative to saline-treated control values for each time point and represent mean values ± SD. siRNA, small interfering RNA.
Figure 5 Activity is maintained upon repeat administration of LNP01. C57BL/6 mice ( n = 5) received a bolus intravenous (IV) injection of either saline, LNP01-formulated control siRNA (siCont) at 5 mg/kg, or LNP01-formulated Factor VII targeting siRNA (siFVII) at 5 mg/kg. Serum samples were collected at various time points and Factor VII protein ­ levels were determined in the samples. After recovery of Factor VII levels to baseline values, animals were redosed on the indicated days. Data were collected for three treatment cycles. Data are displayed as relative to saline-treated control values for each time point and represent mean values ± SD. siRNA, small interfering RNA.CC-BY-NC-ND · From the PDF

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Research works printed but not linked: 38

  1. Soutschek, 2004, Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs, Nature, 432, 173, 10.1038/nature03121 · DOI
  2. de Fougerolles, 2007, Interfering with disease: a progress report on siRNA-based therapeutics, Nat Rev Drug Discov, 6, 443, 10.1038/nrd2310 · DOI
  3. Novina, 2004, The RNAi revolution, Nature, 430, 161, 10.1038/430161a · DOI
  4. Check, 2005, Gene therapy put on hold as third child develops cancer, Nature, 433, 561
  5. Boyce, 2001, Trial halted after gene shows up in semen, Nature, 414, 677, 10.1038/414677a · DOI
  6. Zhang, 2007, Cationic lipids and polymers mediated vectors for delivery of siRNA, J Control Release, 123, 1, 10.1016/j.jconrel.2007.07.016 · DOI
  7. Wagner, 2004, Targeted nucleic acid delivery into tumors: new avenues for cancer therapy, Biomed Pharmacother, 58, 152, 10.1016/j.biopha.2004.01.003 · DOI
  8. Liu, 2002, Development of non-viral vectors for systemic gene delivery, J Control Release, 78, 259, 10.1016/S0168-3659(01)00494-1 · DOI
  9. Li, 2007, Lipid-based nanoparticles for nucleic acid delivery, Pharm Res, 24, 438, 10.1007/s11095-006-9180-5 · DOI
  10. Panyam, 2003, Biodegradable nanoparticles for drug and gene delivery to cells and tissue, Adv Drug Deliv Rev, 55, 329, 10.1016/S0169-409X(02)00228-4 · DOI
  11. Song, 2003, RNA interference targeting Fas protects mice from fulminant hepatitis, Nat Med, 9, 347, 10.1038/nm828 · DOI
  12. Song, 2005, Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors, Nat Biotech, 23, 709, 10.1038/nbt1101 · DOI
  13. Morrissey, 2005, Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs, Nat Biotech, 23, 1002, 10.1038/nbt1122 · DOI
  14. Kim, 2007, Systemic and specific delivery of small interfering RNAs to the liver mediated by apolipoprotein A-I, Mol Ther, 15, 1145, 10.1038/sj.mt.6300168 · DOI
  15. Baigude, 2007, Design and creation of new nanomaterials for therapeutic RNAi, ACS Chem Biol, 2, 237, 10.1021/cb7000582 · DOI
  16. Santel, 2006, A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium, Gene Ther, 13, 1222, 10.1038/sj.gt.3302777 · DOI
  17. Hu-Lieskovan, 2005, Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing's sarcoma, Cancer Res, 65, 8984, 10.1158/0008-5472.CAN-05-0565 · DOI
  18. Takeshita, 2005, Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo, Proc Natl Acad Sci USA, 102, 12177, 10.1073/pnas.0501753102 · DOI
  19. Rozema, 2007, Dynamic PolyConjugates for targeted in vivo delivery of siRNA to hepatocytes, Proc Natl Acad Sci USA, 104, 12982, 10.1073/pnas.0703778104 · DOI
  20. Peer, 2008, Systemic leukocyte-directed siRNA delivery revealing Cyclin D1 as an anti-inflammatory target, Science, 319, 627, 10.1126/science.1149859 · DOI
  21. Wolfrum, 2007, Mechanisms and optimization of in vivo delivery of lipophilic siRNAs, Nat Biotech, 25, 1149, 10.1038/nbt1339 · DOI · Paper page
  22. de Fougerolles, 2008, Delivery vehicles for small interfering RNA in vivo, Human Gene Ther, 19, 125, 10.1089/hum.2008.928 · DOI
  23. Wisse, 2008, The size of endothelial fenestrae in human liver sinusoids: implications for hepatocyte-directed gene transfer, Gene Ther, 15, 1193, 10.1038/gt.2008.60 · DOI
  24. Medina-Kauwe, 2005, Intracellular trafficking of nonviral vectors, Gene Ther, 12, 1734, 10.1038/sj.gt.3302592 · DOI
  25. Wattiaux, 2000, Endosomes, lysosomes: their implication in gene transfer, Adv Drug Deliv Rev, 41, 201, 10.1016/S0169-409X(99)00066-6 · DOI
  26. Mui, 2000, Membrane perturbation and the mechanism of lipid-mediated transfer of DNA into cells, Biochim Biophys Acta, 1467, 281, 10.1016/S0005-2736(00)00226-1 · DOI
  27. Sonawane, 2003, Chloride accumulation and swelling in endosomes enhances DNA transfer by polyamine-DNA polyplexes, J Biol Chem, 278, 44826, 10.1074/jbc.M308643200 · DOI
  28. Satija, 2007, Pharmaceutical and biomedical potential of surface engineered dendrimers, Crit Rev Ther Drug Carrier Syst, 24, 257, 10.1615/CritRevTherDrugCarrierSyst.v24.i3.20 · DOI
  29. Akinc, 2008, A combinatorial library of lipid-like materials for delivery of RNAi therapeutics, Nat Biotech, 26, 561, 10.1038/nbt1402 · DOI · Paper page
  30. Abraham, 2005, The liposomal formulation of doxorubicin, Methods Enzymol, 391, 71, 10.1016/S0076-6879(05)91004-5 · DOI
  31. Fenske, 2008, Liposomal nanomedicines, Expert Opin Drug Deliv, 5, 25, 10.1517/17425247.5.1.25 · DOI
  32. Maurer, 1999, Lipid-based systems for the intracellular delivery of genetic drugs, Mol Membr Biol, 16, 129, 10.1080/096876899294869 · DOI
  33. Judge, 2005, Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA, Nat Biotechnol, 23, 457, 10.1038/nbt1081 · DOI
  34. Semple, 2001, Efficient encapsulation of antisense oligonucleotides in lipid vesicles using ionizable aminolipids: formation of novel small multilamellar vesicle structures, Biochim Biophys Acta, 1510, 152, 10.1016/S0005-2736(00)00343-6 · DOI · Paper page
  35. Wheeler, 1999, Stabilized plasmid-lipid particles: construction and characterization, Gene Ther, 6, 271, 10.1038/sj.gt.3300821 · DOI
  36. Immordino, 2006, Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential, Int J Nanomedicine, 1, 297
  37. Adlakha-Hutcheon, 1999, Controlled destabilization of a liposomal drug delivery system enhances mitoxantrone antitumor activity, Nature Biotech, 17, 775, 10.1038/11710 · DOI
  38. Webb, 1998, Comparison of different hydrophobic anchors conjugated to poly(ethylene glycol): effects on the pharmacokinetics of liposomal vincristine, Biochim Biophys Acta, 1372, 272, 10.1016/S0005-2736(98)00077-7 · DOI

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Metadata

Authors
Akinc, A., Goldberg, M., Qin, J., Dorkin, J. R., Gamba-Vitalo, C., Maier, M., Jayaprakash, K. N., Jayaraman, M., Rajeev, K. G., Manoharan, M., Koteliansky, V., Röhl, I., Leshchiner, E. S., Langer, R., & Anderson, D. G.
Venue
Molecular Therapy
Publisher
Elsevier BV
Published
2009-05
Volume
17
Issue
5
Pages
872-879
ISSN
1525-0016
DOI
10.1038/mt.2009.36
Cited by
323
References
3
Language
en
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