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Despite the extraordinary therapeutic potential of\nthis approach, the need for an efficient gene carrier is hampering the translation of the RNAi technology\nto the clinical setting. Although a diversity of nanocarriers has been described, liposomes continue\nto be one of the most attractive siRNA vehicles due to their relatively low toxicity, facilitated siRNA\ncomplexation, high transfection efficiency and enhanced pharmacokinetic properties.\n&lt;\/P&gt;&lt;P&gt;\nThis review focuses on RNAi as a therapeutic approach, the challenges to its application, namely the\nnucleic acids\u2019 delivery process, and current strategies to improve therapeutic efficacy. Additionally,\nlipid-based nanocarriers are described, and lessons learned from the relation between biophysical\nproperties and biological performance of the dioctadecyldimethylammonium:monoolein (DODAX:\nMO) system are explored.\n&lt;\/P&gt;&lt;P&gt;\nLiposomes show great potential as siRNA delivery systems, being safe nanocarriers to protect nucleic\nacids in circulation, extend their half-life time, target specific cells and reduce off-target effects. Nevertheless,\nseveral issues related to delivery must be overcome before RNAi therapies reach their full\npotential, namely target-cell specificity and endosomal escape. Understanding the relationship between\nbiophysical properties and biological performance is an essential step in the gene therapy field.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1389450119666180703145410","type":"journal-article","created":{"date-parts":[[2018,11,28]],"date-time":"2018-11-28T07:14:50Z","timestamp":1543389290000},"page":"29-50","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Lipid-based Nanocarriers for siRNA Delivery: Challenges, Strategies and the Lessons Learned from the DODAX: MO Liposomal System"],"prefix":"10.2174","volume":"20","author":[{"given":"Ana C.N.","family":"Oliveira","sequence":"first","affiliation":[{"name":"CBMA (Center of Molecular and Environmental Biology), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"given":"Joana","family":"Fernandes","sequence":"additional","affiliation":[{"name":"CBMA (Center of Molecular and Environmental Biology), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"given":"Anabela","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"CBMA (Center of Molecular and Environmental Biology), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"given":"Andreia C.","family":"Gomes","sequence":"additional","affiliation":[{"name":"CBMA (Center of Molecular and Environmental Biology), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"given":"M.E.C.D. 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