title: Synthesis and evaluation of novel lipopeptide as a vehicle for efficient gene delivery and gene silencing.
abstract: Nucleic acid-based therapeutics have recently emerged as a new class of next generation agents for treatment and prevention of viral infection, cancer, and genetic disorders, but their wide use is limited by their relatively weak delivery into target cells. Usage of synthetic cationic amphiphiles with peptide hydrophilic domain as agents for non-viral gene delivery is an attractive approach. We developed the schemes for the synthesis of aliphatic peptides with different length of the hydrocarbon chains in hydrophobic domains and different amino acids in polar head. For the obtained derivatives we determined transfection efficiency, critical vesicle concentration, particle size, ζ-potential and aggregates stability. We have found that the transfection efficiency is increased if the ornithine is a part of polar head in an amphiphile. The most promising amphiphile for liposomal formation OrnOrnGlu(C16H33)2 was examined more carefully. It has been shown that the lipopeptide possesses low toxicity (in vitro and in vivo) and high transfection efficiency with pDNA and siRNA in different cell lines. In addition, the production of liposomes based on this lipopeptide is simple, quick and cheap. Thus OrnOrnGlu(C16H33)2 is a promising vehicle for gene delivery and gene silencing.
authors.affiliation: Lomonosov Moscow State University of Fine Chemical Technologies, Moscow, Russia; NRC Institute of Immunology, FMBA, Moscow, Russia. Electronic address: oo.koloskova@nrcii.ru.
authors.forename: O O
authors.initials: OO
authors.lastname: Koloskova
authors.affiliation: NRC Institute of Immunology, FMBA, Moscow, Russia; Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Nikonova
authors.affiliation: Lomonosov Moscow State University of Fine Chemical Technologies, Moscow, Russia.
authors.forename: U A
authors.initials: UA
authors.lastname: Budanova
authors.affiliation: NRC Institute of Immunology, FMBA, Moscow, Russia.
authors.forename: I P
authors.initials: IP
authors.lastname: Shilovskiy
authors.affiliation: NRC Institute of Immunology, FMBA, Moscow, Russia.
authors.forename: I A
authors.initials: IA
authors.lastname: Kofiadi
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Ivanov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: O A
authors.initials: OA
authors.lastname: Smirnova
authors.affiliation: Mechnikov Research Institute of Vaccines and Sera, Moscow, Russia.
authors.forename: V V
authors.initials: VV
authors.lastname: Zverev
authors.affiliation: Lomonosov Moscow State University of Fine Chemical Technologies, Moscow, Russia.
authors.forename: Yu L
authors.initials: YL
authors.lastname: Sebaykin
authors.affiliation: NRC Institute of Immunology, FMBA, Moscow, Russia.
authors.forename: S M
authors.initials: SM
authors.lastname: Andreev
authors.affiliation: NRC Institute of Immunology, FMBA, Moscow, Russia.
authors.forename: M R
authors.initials: MR
authors.lastname: Khaitov
mesh_terms: D000072283:A549 Cells; D000818:Animals; D016466:CHO Cells; D002412:Cations / Q000008:administration & dosage / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D003412:Cricetulus; D004247:DNA / Q000378:metabolism; D020868:Gene Silencing / Q000187:drug effects*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D019169:Jurkat Cells; D055666:Lipopeptides / Q000008:administration & dosage* / Q000737:chemistry*; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism; D014162:Transfection / Q000379:methods
chemical_list: D002412:Cations; D055666:Lipopeptides; D008081:Liposomes; D034741:RNA, Small Interfering; D004247:DNA
keywords: DNA; Lipopeptides; Transfection; siRNA