Skip to main content

A Multifunctional Envelope-Type Nano Device Containing a pH-Sensitive Cationic Lipid for Efficient Delivery of Short Interfering RNA to Hepatocytes In Vivo

  • Protocol
SiRNA Delivery Methods

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1364))

Abstract

Various types of nanoparticles have been developed with the intent of efficiently delivering short interfering RNA (siRNA) to hepatocytes to date. To achieve efficient SiRNA delivery, various aspects of the delivery processes and physical properties need to be considered. We recently developed an original lipid nanoparticle, a multifunctional envelope-type nano device (MEND) containing YSK05, a pH-sensitive cationic lipid (YSK05-MEND). The YSK05-MEND with SiRNA in its formulation showed hepatocyte-specific uptake and robust gene silencing in hepatocytes after intravenous administration. Here, we describe the procedure used in the preparation and characterization method of the YSK05-MEND.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494–498

    Article  CAS  PubMed  Google Scholar 

  2. McClellan J, King MC (2010) Genetic heterogeneity in human disease. Cell 141:210–217

    Article  CAS  PubMed  Google Scholar 

  3. Adami RC, Seth S, Harvie P, Johns R, Fam R, Fosnaugh K, Zhu TY, Farber K, McCutcheon M, Goodman TT, Liu Y, Chen Y, Kwang E, Templin MV, Severson G, Brown T, Vaish N, Chen F, Charmley P, Polisky B, Houston ME (2011) An amino acid-based amphoteric liposomal delivery system for systemic administration of siRNA. Mol Ther 19:1141–1151

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Semple SC, Akinc A, Chen JX, Sandhu AP, Mui BL, Cho CK, Sah DWY, Stebbing D, Crosley EJ, Yaworski E, Hafez IM, Dorkin JR, Qin J, Lam K, Rajeev KG, Wong KF, Jeffs LB, Nechev L, Eisenhardt ML, Jayaraman M, Kazem M, Maier MA, Srinivasulu M, Weinstein MJ, Chen QM, Alvarez R, Barros SA, De S, Klimuk SK, Borland T, Kosovrasti V, Cantley WL, Tam YK, Manoharan M, Ciufolini MA, Tracy MA, de Fougerolles A, MacLachlan I, Cullis PR, Madden TD, Hope MJ (2010) Rational design of cationic lipids for siRNA delivery. Nat Biotechnol 28:172–176

    Article  CAS  PubMed  Google Scholar 

  5. Love KT, Mahon KP, Levins CG, Whitehead KA, Querbes W, Dorkin JR, Qin J, Cantley W, Qin LL, Racie T, Frank-Kamenetsky M, Yip KN, Alvarez R, Sah DWY, de Fougerolles A, Fitzgerald K, Koteliansky V, Akinc A, Langer R, Anderson DG (2010) Lipid-like materials for low-dose, in vivo gene silencing. Proc Natl Acad Sci U S A 107:1864–1869

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Wooddell CI, Rozema DB, Hossbach M, John M, Hamilton HL, Chu QL, Hegge JO, Klein JJ, Wakefield DH, Oropeza CE, Deckert J, Roehl I, Jahn-Hofmann K, Hadwiger P, Vornlocher HP, McLachlan A, Lewis DL (2013) Hepatocyte-targeted RNAi therapeutics for the treatment of chronic hepatitis B virus infection. Mol Ther 21:973–985

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Sato Y, Hatakeyama H, Sakurai Y, Hyodo M, Akita H, Harashima H (2012) A pH-sensitive cationic lipid facilitates the delivery of liposomal siRNA and gene silencing activity in vitro and in vivo. J Control Release 163:267–276

    Article  CAS  PubMed  Google Scholar 

  8. Jayaraman M, Ansell SM, Mui BL, Tam YK, Chen JX, Du XY, Butler D, Eltepu L, Matsuda S, Narayanannair JK, Rajeev KG, Hafez IM, Akinc A, Maier MA, Tracy MA, Cullis PR, Madden TD, Manoharan M, Hope MJ (2012) Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo. Angew Chem Int Ed Engl 51:8529–8533

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Jacobs F, Wisse E, De Geest B (2010) The role of liver sinusoidal cells in hepatocyte-directed gene transfer. Am J Pathol 176:14–21

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Watanabe T, Hatakeyama H, Matsuda-Yasui C, Sato Y, Sudoh M, Takagi A, Hirata Y, Ohtsuki T, Arai M, Inoue K, Harashima H, Kohara M (2014) In vivo therapeutic potential of Dicer-hunting siRNAs targeting infectious hepatitis C virus. Sci Rep 4

    Google Scholar 

  11. Hatakeyama H, Murata M, Sato Y, Takahashi M, Minakawa N, Matsuda A, Harashima H (2014) The systemic administration of an anti-miRNA oligonucleotide encapsulated pH-sensitive liposome results in reduced level of hepatic microRNA-122 in mice. J Control Release 173:43–50

    Article  CAS  PubMed  Google Scholar 

  12. Hayashi Y, Suemitsu E, Kajimoto K, Sato Y, Akhter A, Sakurai Y, Hatakeyama H, Hyodo M, Kaji N, Baba Y, Harashima H (2014) Hepatic monoacylglycerol O-acyltransferase 1 as a promising therapeutic target for steatosis, obesity, and type 2 diabetes. Mol Ther Nucleic Acids 3:e154

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgement

This work was supported in parts by grants from the Special Education and Research Expenses of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and a Grants-in-Aid for Research Activity Start-up from the Japan Society for Promotion of Science (JSPS). The authors also wish to thank Dr. Milton S. Feather for his helpful advice in writing the English manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michinori Kohara .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Sato, Y., Harashima, H., Kohara, M. (2016). A Multifunctional Envelope-Type Nano Device Containing a pH-Sensitive Cationic Lipid for Efficient Delivery of Short Interfering RNA to Hepatocytes In Vivo. In: Shum, K., Rossi, J. (eds) SiRNA Delivery Methods. Methods in Molecular Biology, vol 1364. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3112-5_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-3112-5_7

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3111-8

  • Online ISBN: 978-1-4939-3112-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics