A new genomic editing strategy using lipid nanoparticles with spherical nucleic acids and CRISPR

 

CRISPR-Cas systems are a recently discovered biological tool that functions like “molecular scissors,” capable of locating and cutting specific fragments of DNA to modify or correct them with great precision. This gene-editing machinery has transformed biology by offering the possibility of correcting genetic errors.

However, one of its main challenges has been transporting the editing machinery safely and efficiently into cells, since traditional methods—such as viral vectors or lipid nanoparticles (LNPs)—often present issues like toxicity, low efficiency, or immune reactions.

A recent study proposes an innovative solution by encapsulating the CRISPR-Cas machinery inside lipid nanoparticles coated with spherical nucleic acids (SNAs), resulting in nanostructures of approximately 130 nm in size. The outer DNA layer facilitates entry into cells, while the lipid core stabilizes the CRISPR-Cas system and enables its controlled release. The lipid nanostructure includes both the plasmids that encode the CRISPR machinery, and the templates required for DNA repair by means of the HDR (homology-directed repair) pathway.

In summary, this design allows for improved cellular uptake of the nanoparticle, which in turn delivers the CRISPR-Cas machinery. It reduces toxicity and increases gene-editing efficiency.

The research team tested this strategy using different cell types and evaluating how many nanoparticles successfully entered the cells, if there were toxic effects, and whether the CRISPR machinery was effectively delivered. They then analyzed the cellular DNA to confirm if CRISPR had produced the expected edits.

The results showed that this system not only generated the typical nucleotide deletion edits but also enabled precise repairs by means of the HDR pathway. Compared with conventional LNPs, the new structures were more efficient, showed no toxicity, and maintained high cell viability even at elevated concentrations.

The researchers emphasized that these hybrid nanoparticles, called LNP-SNAs, could in the future be adapted to target specific organs. Thanks to their greater safety and efficacy, CRISPR-LNP-SNAs represent a versatile and scalable platform that brings gene-editing therapies closer to clinical application.

For further details, see: PNAS