Flash nanoprecipitation assisted self-assembly of ionizable lipid nanoparticles for nucleic acid delivery

Mar 21, 2024Nanoscale

Using rapid mixing to create charged lipid nanoparticles for delivering genetic material

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Abstract

FNP-assembled lipid nanoparticles achieved >95% encapsulation efficiency for mRNA and siRNA payloads.

Ionizable lipid nanoparticles (LNPs) can effectively deliver nucleic acids into cells.
LNPs prepared with SM102 or ALC0315 successfully delivered mRNA to immune cells and lymphoid organs.
LNPs utilizing DLin-MC3-DMA facilitated effective delivery of intracellular siRNA with significant functionality.
The flash nanoprecipitation method allows for the economical production of LNPs in smaller volumes, suitable for early-stage research.

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Ionizable lipid nanoparticles (LNPs) have emerged as a powerful tool for the intracellular delivery of nucleic acids. Following the recent success of LNP-based siRNA therapeutics and mRNA vaccines, the use of ionizable lipids for nucleic acid delivery has tremendously increased. Here, we introduce a flash nanoprecipitation (FNP) approach using the confined impingement (CIJ) mixer to stably self-assemble ionizable LNPs. To validate this approach, we employed three clinically relevant LNP formulations containing SM102, ALC0315, and DLin-MC3-DMA as ionizable lipids. FNP-assembled LNPs showed >95% encapsulation efficiency of mRNA and siRNA payloads and particle sizes below 150 nm. SM102 or ALC0315 LNPs demonstrated efficient delivery of mRNA into immune cellsand to lymphoid organs, whereas Dlin-MC3-DMA LNPs allowed effective intracellular siRNA delivery with great functional ability. The FNP technique could economically produce LNPs in smaller volumes that are highly suitable for the discovery phase. in vitro in vivo

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Flash nanoprecipitation assisted self-assembly of ionizable lipid nanoparticles for nucleic acid delivery

Abstract

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