2. Academic Validation
  3. Novel macrocyclic and acyclic cationic lipids for gene transfer: synthesis and in vitro evaluation

Novel macrocyclic and acyclic cationic lipids for gene transfer: synthesis and in vitro evaluation

  • Bioorg Med Chem Lett. 2012 Jul 15;22(14):4686-92. doi: 10.1016/j.bmcl.2012.05.080.
William P D Goldring 1,  Emile Jubeli,  Rachael A Downs,  Adam J S Johnston,  Nada Abdul Khalique,  Liji Raju,  Deena Wafadari,  Michael D Pungente
Affiliations

Affiliation

  • 1 School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast, Northern Ireland, BT9 5AG, United Kingdom. w.goldring@qub.ac.uk
PMID: 22704922 DOI: 10.1016/j.bmcl.2012.05.080
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).

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