Newly Developed DNA-Wrapped Nanoparticles Enhance CRISPR Delivery

Researchers at Northwestern University have developed a new type of nanostructure that improves the delivery of CRISPR gene-editing tools into cells. The innovation centers on lipid nanoparticle spherical nucleic acids (LNP-SNAs), which are small particles containing the full suite of CRISPR machinery—Cas9 enzyme, guide RNA, and DNA repair templates—encased in a dense shell of DNA. This unique DNA shell not only protects the CRISPR tools but also enables targeted delivery to specific organs and tissues, enhancing cellular uptake.

Testing across human and animal cell types demonstrated that LNP-SNAs enter cells up to three times more efficiently than standard lipid nanoparticles used in COVID-19 vaccines, produce less toxicity, and raise gene-editing efficiency by threefold. They also increase the rate of precise DNA repairs by over 60% compared to current techniques. These findings, to be published in the Proceedings of the National Academy of Sciences, highlight how a nanomaterial’s structure—not just its ingredients—is crucial for effectiveness. This concept forms the foundation of structural nanomedicine, an emerging field pioneered by Chad A. Mirkin and his team.

Mirkin, the study’s senior author, explained, “CRISPR is an incredibly powerful tool that could correct defects in genes to decrease susceptibility to disease and even eliminate disease itself. But it’s difficult to get CRISPR into the cells and tissues that matter.” The problem lies in the inability of CRISPR machinery to enter cells unaided; current delivery methods like viral vectors can spark immune reactions, while regular lipid nanoparticles often fail to enter the cell’s nucleus, reducing their effectiveness.

To overcome these barriers, Mirkin’s lab utilized spherical nucleic acids (SNAs), which are globular forms of DNA and RNA that naturally penetrate cells. Their surface, covered in DNA strands, interacts with cell receptors to promote uptake and can be engineered to target specific cell types. “Simple changes to the particle’s structure can dramatically change how well a cell takes it up,” said Mirkin. Seven SNA-based therapies are already in clinical trials, pointing to the versatility of this approach.

In trials, LNP-SNAs with CRISPR cargo successfully modified the DNA of skin cells, white blood cells, bone marrow stem cells, and kidney cells. The system excelled at cellular entry and genetic editing with minimal toxicity. Future research will validate this technology in disease models. Mirkin concludes, “By marrying two powerful biotechnologies—CRISPR and SNAs—we have created a strategy that could unlock CRISPR’s full therapeutic potential.”