Frontiers in genome editingOct 1, 2026

Using lysine-based lipid nanoparticles to improve delivery of large all-in-one CRISPR/Cas9 gene-editing tools

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Oct 2, 2026

Abstract

K3C16 was successfully engineered as the main lipid component of lipid nanoparticles for the first time.

Lipid nanoparticles (LNPs) are utilized for delivering gene-editing tools like the CRISPR/Cas9 system.
K3C16, a lysine-headgroup cationic lipid, has shown high biocompatibility and effective cellular uptake.
The study demonstrates the potential of K3C16 in a multi-component LNP matrix for large cargo encapsulation.
This work highlights the feasibility of using K3C16 in developing low-toxicity gene delivery systems.

Simplified

Lipid nanoparticles (LNPs) are widely used as drug delivery systems (DDS) for the intracellular delivery of gene-editing tools such as the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system. Previously, a lysine-headgroup cationic lipid (K3C16) was reported to exhibit high biocompatibility and cellular internalization via plasma membrane fusion when formulated as liposomes, suggesting its potential as a low-toxicity gene delivery material. However, the translation of this lipid into a multi-component lipid nanoparticle (LNP) matrix via microfluidic engineering for large cargo encapsulation has not been explored. In this study, K3C16 was successfully engineered for the first time as the main lipid component of LNPs to deliver large plasmid DNA encoding the CRISPR/Cas9 system.

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Using lysine-based lipid nanoparticles to improve delivery of large all-in-one CRISPR/Cas9 gene-editing tools

Abstract

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