Novel macrocyclic and acyclic cationic lipids for gene transfer

Synthesis and in vitro evaluation

W. P. D. Goldring, E. Jubeli, R. A. Downs, A. J. S. Johnston, N. A. Khalique, L. Raju, D. Wafadari, M. D. Pungente

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

The synthesis and in vitro evaluation of four cationic lipid gene delivery vectors, characterized by acyclic or macrocyclic, and saturated or unsaturated hydrophobic regions, is described. The synthesis employed standard protocols, including ring-closing metathesis for macrocyclic lipid construction. All lipoplexes studied, formulated from plasmid DNA and a liposome composed of a synthesized lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC), and either 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol as co-lipid, exhibited plasmid DNA binding and protection from DNase I degradation, and concentration dependent cytotoxicity using Chinese hamster ovary-K1 cells. The transfection efficiency of formulations with cholesterol outperformed those with DOPE, and in many cases the EPC/cholesterol control, and formulations with a macrocyclic lipid (+/− 10:1) outperformed their acyclic counterparts (+/− 3:1).
OriginalsprogEngelsk
TidsskriftBioorganic & Medicinal Chemistry Letters
Vol/bind22
Udgave nummer14
Sider (fra-til)4686-4692
Antal sider7
ISSN0960-894X
DOI
StatusUdgivet - 2012
Udgivet eksterntJa

Citer dette

Goldring, W. P. D. ; Jubeli, E. ; Downs, R. A. ; Johnston, A. J. S. ; Khalique, N. A. ; Raju, L. ; Wafadari, D. ; Pungente, M. D. / Novel macrocyclic and acyclic cationic lipids for gene transfer : Synthesis and in vitro evaluation. I: Bioorganic & Medicinal Chemistry Letters. 2012 ; Bind 22, Nr. 14. s. 4686-4692.
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title = "Novel macrocyclic and acyclic cationic lipids for gene transfer: Synthesis and in vitro evaluation",
abstract = "The synthesis and in vitro evaluation of four cationic lipid gene delivery vectors, characterized by acyclic or macrocyclic, and saturated or unsaturated hydrophobic regions, is described. The synthesis employed standard protocols, including ring-closing metathesis for macrocyclic lipid construction. All lipoplexes studied, formulated from plasmid DNA and a liposome composed of a synthesized lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC), and either 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol as co-lipid, exhibited plasmid DNA binding and protection from DNase I degradation, and concentration dependent cytotoxicity using Chinese hamster ovary-K1 cells. The transfection efficiency of formulations with cholesterol outperformed those with DOPE, and in many cases the EPC/cholesterol control, and formulations with a macrocyclic lipid (+/− 10:1) outperformed their acyclic counterparts (+/− 3:1).",
author = "Goldring, {W. P. D.} and E. Jubeli and Downs, {R. A.} and Johnston, {A. J. S.} and Khalique, {N. A.} and L. Raju and D. Wafadari and Pungente, {M. D.}",
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Goldring, WPD, Jubeli, E, Downs, RA, Johnston, AJS, Khalique, NA, Raju, L, Wafadari, D & Pungente, MD 2012, 'Novel macrocyclic and acyclic cationic lipids for gene transfer: Synthesis and in vitro evaluation', Bioorganic & Medicinal Chemistry Letters, bind 22, nr. 14, s. 4686-4692. https://doi.org/10.1016/j.bmcl.2012.05.080

Novel macrocyclic and acyclic cationic lipids for gene transfer : Synthesis and in vitro evaluation. / Goldring, W. P. D.; Jubeli, E.; Downs, R. A.; Johnston, A. J. S.; Khalique, N. A.; Raju, L.; Wafadari, D.; Pungente, M. D.

I: Bioorganic & Medicinal Chemistry Letters, Bind 22, Nr. 14, 2012, s. 4686-4692.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Novel macrocyclic and acyclic cationic lipids for gene transfer

T2 - Synthesis and in vitro evaluation

AU - Goldring, W. P. D.

AU - Jubeli, E.

AU - Downs, R. A.

AU - Johnston, A. J. S.

AU - Khalique, N. A.

AU - Raju, L.

AU - Wafadari, D.

AU - Pungente, M. D.

PY - 2012

Y1 - 2012

N2 - The synthesis and in vitro evaluation of four cationic lipid gene delivery vectors, characterized by acyclic or macrocyclic, and saturated or unsaturated hydrophobic regions, is described. The synthesis employed standard protocols, including ring-closing metathesis for macrocyclic lipid construction. All lipoplexes studied, formulated from plasmid DNA and a liposome composed of a synthesized lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC), and either 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol as co-lipid, exhibited plasmid DNA binding and protection from DNase I degradation, and concentration dependent cytotoxicity using Chinese hamster ovary-K1 cells. The transfection efficiency of formulations with cholesterol outperformed those with DOPE, and in many cases the EPC/cholesterol control, and formulations with a macrocyclic lipid (+/− 10:1) outperformed their acyclic counterparts (+/− 3:1).

AB - The synthesis and in vitro evaluation of four cationic lipid gene delivery vectors, characterized by acyclic or macrocyclic, and saturated or unsaturated hydrophobic regions, is described. The synthesis employed standard protocols, including ring-closing metathesis for macrocyclic lipid construction. All lipoplexes studied, formulated from plasmid DNA and a liposome composed of a synthesized lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC), and either 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol as co-lipid, exhibited plasmid DNA binding and protection from DNase I degradation, and concentration dependent cytotoxicity using Chinese hamster ovary-K1 cells. The transfection efficiency of formulations with cholesterol outperformed those with DOPE, and in many cases the EPC/cholesterol control, and formulations with a macrocyclic lipid (+/− 10:1) outperformed their acyclic counterparts (+/− 3:1).

U2 - 10.1016/j.bmcl.2012.05.080

DO - 10.1016/j.bmcl.2012.05.080

M3 - Journal article

VL - 22

SP - 4686

EP - 4692

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

SN - 0960-894X

IS - 14

ER -