A research team at Northwestern University has developed a novel lipid nanoparticle spherical nucleic acid (LNP-SNA) that can significantly improve the delivery efficiency and safety of the CRISPR gene editing system. The study, led by Chemistry Professor Chad A. Mirkin, was published in the Proceedings of the National Academy of Sciences.
The main challenge facing CRISPR gene editing technology is how to safely and efficiently deliver the editing tools to target cells. Existing viral vectors easily trigger immune responses, while lipid nanoparticles (LNPs), although relatively safe, have limited efficiency. The LNP-SNAs designed by the Northwestern University team encapsulate the full set of CRISPR components (including Cas9 enzyme, guide RNA, and DNA repair template) with a dense DNA shell. This not only protects the editing tools but also enhances cell targeting and uptake efficiency through structural design.
Experiments showed that LNP-SNAs achieved three times the delivery efficiency of traditional LNP systems in human skin cells, white blood cells, bone marrow stem cells, and kidney cells, with significantly reduced cytotoxicity and a gene editing success rate increased by more than 60%. Mirkin stated: "By using SNAs to deliver the mechanisms required for gene editing, our goal is to maximize the efficiency of CRISPR and expand the number of cell and tissue types to which we can deliver CRISPR."
This technology is based on the principles of structural nanomedicine, emphasizing the influence of nanomaterial structure rather than composition on function. The DNA shell of LNP-SNAs can specifically bind to cell surface receptors, promoting active cellular internalization and preventing the editing tools from being trapped in endosomes. Currently, Northwestern University's spin-off company Flashpoint Therapeutics has advanced SNA-based therapies into Phase II clinical trials for diseases such as Merkel cell carcinoma.
Mirkin noted: "CRISPR has the potential to transform the entire field of medicine, but how we design the delivery vehicle is just as important as the gene tool itself. By combining two powerful biotechnologies — CRISPR and SNAs — we have created a strategy that can unleash the full therapeutic potential of CRISPR." The team's next step is to validate the platform's in vivo application potential in various disease models.
