Novel Cationic Carotenoid Lipids as Delivery Vectors of Antisense Oligonucleotides for Exon Skipping in Duchenne Muscular Dystrophy

Abstract

Duchenne Muscular Dystrophy (DMD) is a common, inherited, incurable, fatal muscle wasting disease caused by deletions that disrupt the reading frame of the DMD gene such that no functional dystrophin protein is produced. Antisense oligonucleotide (AO)-directed exon skipping restores the reading frame of the DMD gene, and truncated, yet functional dystrophin protein is expressed. The aim of this study was to assess the efficiency of two novel rigid, cationic carotenoid lipids, C30-20 and C20-20, in the delivery of a phosphorodiamidate morpholino (PMO) AO, specifically designed for the targeted skipping of exon 45 of DMD mRNA in normal human skeletal muscle primary cells (hSkMCs). The cationic carotenoid lipid/PMO-AO lipoplexes yielded significant exon 45 skipping relative to a known commercial lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC).

Superlative carotenoids.

“…The length of the alkyl chain modifies the efficiency of the carrier. The results so far obtained confirm the validity of the concept (Popplewell et al, 2012).…”

Hydrophilic Carotenoids: Recent Progress

“…Very recently Sliwka et al . synthetized some new cationic carotenoid lipids, where a quaternary ammonium moiety is responsible for the amphipatic character of the molecules [12,13].…”

Bioactive Compounds from Biomass

“…23 Carotenoids are thought to be active agents for the prevention of cancer, 24 cardiovascular diseases, 25 and muscular degeneration. 26 …”