Cationic liposome-nucleic acid complexes for gene delivery and silencing: Pathways and mechanisms for plasmid DNA and siRNA

Kai K. Ewert; Alexandra Zidovska; Ayesha Ahmad; Nathan F. Bouxsein; Heather M. Evans; Christopher S. McAllister; Charles E. Samuel; Cyrus R. Safinya

doi:10.1007/128_2010_70

Cationic liposome-nucleic acid complexes for gene delivery and silencing: Pathways and mechanisms for plasmid DNA and siRNA

Kai K. Ewert, Alexandra Zidovska, Ayesha Ahmad, Nathan F. Bouxsein, Heather M. Evans, Christopher S. McAllister, Charles E. Samuel, Cyrus R. Safinya

Research output: Chapter in Book/Report/Conference proceeding › Chapter

Abstract

Motivated by the promises of gene therapy, there is great interest in developing non-viral lipid-based vectors for therapeutic applications due to their low immunogenicity, low toxicity, ease of production, and the potential of transferring large pieces of DNA into cells. In fact, cationic liposome (CL) based vectors are among the prevalent synthetic carriers of nucleic acids (NAs) currently used in gene therapy clinical trials worldwide. These vectors are studied both for gene delivery with CL-DNA complexes and gene silencing with CL-siRNA (short interfering RNA) complexes. However, their transfection efficiencies and silencing efficiencies remain low compared to those of engineered viral vectors. This reflects the currently poor understanding of transfection-related mechanisms at the molecular and self-assembled levels, including a lack of knowledge about interactions between membranes and double stranded NAs and between CL-NA complexes and cellular components. In this review we describe our recent efforts to improve the mechanistic understanding of transfection by CL-NA complexes, which will help to design optimal lipid-based carriers of DNA and siRNA for therapeutic gene delivery and gene silencing.

Original language	English (US)
Title of host publication	Nucleic Acid Transfection
Editors	Wolfgang Bielke, Christoph Erbacher
Pages	191-226
Number of pages	36
DOIs	https://doi.org/10.1007/128_2010_70
State	Published - 2010

Publication series

Name	Topics in Current Chemistry
Volume	296
ISSN (Print)	0340-1022

Keywords

Cholesterol
Gene delivery
Multivalent cationic lipid
Small angle X-ray scattering
siRNA

ASJC Scopus subject areas

General Chemistry

Access to Document

10.1007/128_2010_70

Cite this

Ewert, K. K., Zidovska, A., Ahmad, A., Bouxsein, N. F., Evans, H. M., McAllister, C. S., Samuel, C. E., & Safinya, C. R. (2010). Cationic liposome-nucleic acid complexes for gene delivery and silencing: Pathways and mechanisms for plasmid DNA and siRNA. In W. Bielke, & C. Erbacher (Eds.), Nucleic Acid Transfection (pp. 191-226). (Topics in Current Chemistry; Vol. 296). https://doi.org/10.1007/128_2010_70

Cationic liposome-nucleic acid complexes for gene delivery and silencing: Pathways and mechanisms for plasmid DNA and siRNA. / Ewert, Kai K.; Zidovska, Alexandra; Ahmad, Ayesha et al.
Nucleic Acid Transfection. ed. / Wolfgang Bielke; Christoph Erbacher. 2010. p. 191-226 (Topics in Current Chemistry; Vol. 296).

Research output: Chapter in Book/Report/Conference proceeding › Chapter

Ewert, KK, Zidovska, A, Ahmad, A, Bouxsein, NF, Evans, HM, McAllister, CS, Samuel, CE & Safinya, CR 2010, Cationic liposome-nucleic acid complexes for gene delivery and silencing: Pathways and mechanisms for plasmid DNA and siRNA. in W Bielke & C Erbacher (eds), Nucleic Acid Transfection. Topics in Current Chemistry, vol. 296, pp. 191-226. https://doi.org/10.1007/128_2010_70

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abstract = "Motivated by the promises of gene therapy, there is great interest in developing non-viral lipid-based vectors for therapeutic applications due to their low immunogenicity, low toxicity, ease of production, and the potential of transferring large pieces of DNA into cells. In fact, cationic liposome (CL) based vectors are among the prevalent synthetic carriers of nucleic acids (NAs) currently used in gene therapy clinical trials worldwide. These vectors are studied both for gene delivery with CL-DNA complexes and gene silencing with CL-siRNA (short interfering RNA) complexes. However, their transfection efficiencies and silencing efficiencies remain low compared to those of engineered viral vectors. This reflects the currently poor understanding of transfection-related mechanisms at the molecular and self-assembled levels, including a lack of knowledge about interactions between membranes and double stranded NAs and between CL-NA complexes and cellular components. In this review we describe our recent efforts to improve the mechanistic understanding of transfection by CL-NA complexes, which will help to design optimal lipid-based carriers of DNA and siRNA for therapeutic gene delivery and gene silencing.",

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author = "Ewert, {Kai K.} and Alexandra Zidovska and Ayesha Ahmad and Bouxsein, {Nathan F.} and Evans, {Heather M.} and McAllister, {Christopher S.} and Samuel, {Charles E.} and Safinya, {Cyrus R.}",

note = "Funding Information: KKE, AZ, AA, NFB, HME, and CRS were supported primarily by NIH GM-59288-11 and in part, by DOE-BES grant DE-FG02-06ER46314 (lipid microstructure) and NSF-DMR 0803103 (lipid phase behavior). CSM and CES were supported by NIH AI-12520 and AI-20611. Cryo-TEM experiments were conducted at the National Resource for Automated Molecular Microscopy which is supported by the National Institutes of Health though the National Center for Research Resources{\textquoteright} P41 program (RR17573). The X-ray diffraction work was carried out at the Stanford Synchrotron Radiation Laboratory which is supported by the Department of Energy.",

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doi = "10.1007/128_2010_70",

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N2 - Motivated by the promises of gene therapy, there is great interest in developing non-viral lipid-based vectors for therapeutic applications due to their low immunogenicity, low toxicity, ease of production, and the potential of transferring large pieces of DNA into cells. In fact, cationic liposome (CL) based vectors are among the prevalent synthetic carriers of nucleic acids (NAs) currently used in gene therapy clinical trials worldwide. These vectors are studied both for gene delivery with CL-DNA complexes and gene silencing with CL-siRNA (short interfering RNA) complexes. However, their transfection efficiencies and silencing efficiencies remain low compared to those of engineered viral vectors. This reflects the currently poor understanding of transfection-related mechanisms at the molecular and self-assembled levels, including a lack of knowledge about interactions between membranes and double stranded NAs and between CL-NA complexes and cellular components. In this review we describe our recent efforts to improve the mechanistic understanding of transfection by CL-NA complexes, which will help to design optimal lipid-based carriers of DNA and siRNA for therapeutic gene delivery and gene silencing.

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Cationic liposome-nucleic acid complexes for gene delivery and silencing: Pathways and mechanisms for plasmid DNA and siRNA

Abstract

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Keywords

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