D-Lin-MC3-DMA is an ionizable lipid with dilinoleyl chains and a pH-sensitive dimethylamino headgroup, notable for its role in advanced lipid nanoparticle formulations. Its carefully tuned chemical design allows efficient RNA encapsulation and enhanced endosomal escape, which has made it a benchmark lipid in nucleic acid delivery research. As a model for next-generation ionizable lipids, it provides a foundation for high-efficiency, biocompatible delivery systems.
Reference Reading
1. In Vitro Inhibition of Replication of Dengue Virus Serotypes 1-4 by siRNAs Bound to Non-Toxic Liposomes
Carlos Andrés Rodriguez-Salazar, Delia Piedad Recalde-Reyes, Juan Pablo Bedoya, Leonardo Padilla-Sanabria, Jhon Carlos Castaño-Osorio, Maria Isabel Giraldo. Viruses. 2022 Feb 7;14(2):339. doi: 10.3390/v14020339.
Dengue virus is a ssRNA+ flavivirus, which produces the dengue disease in humans. Currently, no specific treatment exists. siRNAs regulate gene expression and have been used systematically to silence viral genomes; however, they require controlled release. Liposomes show favorable results encapsulating siRNA for gene silencing. The objective herein was to design and evaluate in vitro siRNAs bound to liposomes that inhibit DENV replication. siRNAs were designed against DENV1-4 from conserved regions using siDirect2.0 and Web-BLOCK-iT™ RNAiDesigner; the initial in vitro evaluation was carried out through transfection into HepG2 cells. siRNA with silencing capacity was encapsulated in liposomes composed of D-Lin-MC3-DMA, DSPC, Chol. Cytotoxicity, hemolysis, pro-inflammatory cytokine release and antiviral activity were evaluated using plaque assay and RT-qPCR. A working concentration of siRNA was established at 40 nM. siRNA1, siRNA2, siRNA3.1, and siRNA4 were encapsulated in liposomes, and their siRNA delivery through liposomes led to a statistically significant decrease in viral titers, yielded no cytotoxicity or hemolysis and did not stimulate release of pro-inflammatory cytokines. Finally, liposomes were designed with siRNA against DENV, which proved to be safe in vitro.
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