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Unsaturated, Trialkyl Ionizable Lipids are Versatile Lipid‐Nanoparticle Components for Therapeutic and Vaccine Applications
Flexible Unsaturated Ionizable Lipids for Use in Therapeutic and Vaccine Nanoparticles
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Abstract
Formulated lipid nanoparticles containing Lipid 10 demonstrate significantly greater gene silencing and improved liver delivery compared to established lipid benchmarks.
- A library of 16 novel ionizable lipids was evaluated for their ability to enhance the delivery of nucleic acid therapeutics.
- Lipid 10, with short, branched trialkyl hydrophobic domains, was identified as a top performer in promoting LNP fusogenicity and potency.
- Lipid 10 encapsulating transthyretin siRNA achieved higher gene silencing efficacy than the benchmark lipid DLin-MC3-DMA while also being better tolerated.
- This lipid also showed superior liver delivery of mRNA compared to other tested ionizable lipids.
- In a rodent vaccine model, Lipid 10 elicited comparable or higher antibody titers than the lipids used in FDA-approved mRNA COVID vaccines.
- These findings indicate that Lipid 10 may be a versatile option for both therapeutic and vaccine applications involving diverse nucleic acid payloads.
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