New nanostructure enhances CRISPR delivery
A new nanostructure offers enhanced delivery of CRISPR gene-editing technology, providing a safer and more precise approach than existing methods.
In a recent study, researchers at Northwestern University (IL, USA) have developed a new type of nanostructure that significantly improves the safety and delivery of CRISPR gene-editing tools into cells. By strategically combining two biotechnologies, their findings may pave the way for safer and more effective CRISPR-based therapies for a wide range of diseases.
CRISPR technology has emerged as a powerful tool in regenerative medicine, enabling the modification of genes to combat various diseases. Typically, viral vectors and lipid nanoparticles (LNP) are used to deliver CRISPR technology into cells, each with their own benefits and limitations. Viral vectors, while effective, can trigger unwanted immune responses in patients and, while lipid nanoparticles are a safer alternative, they can get trapped in cellular compartments, preventing the effective release of their therapeutic materials.
“Only a fraction of the CRISPR machinery actually makes it into the cell and even a smaller fraction makes it all the way into the nucleus,” Chad Mirkin, who led the study, explained. “Another strategy is to remove cells from the body, inject the CRISPR components and then put the cells back in. As you can imagine, that’s extremely inefficient and impractical.”
Wanting to enhance CRISPR delivery into cells, the research team utilized spherical nucleic acids (SNAs) – globular forms of DNA and RNA originally developed in Mirkin’s Lab. These SNAs are designed to surround a nanoparticle core, which can be loaded with therapeutic materials: cas9 enzymes, guide RNA and a DNA repair template. The team then coated an LNP core (containing CRISPR) with a dense layer of short DNA strands, creating a protective shell that significantly improves cellular uptake.
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Importantly, the coated layer of DNA strands not only protected the CRISPR components but was also capable of directing which organs and tissues the LNP-SNAs migrate to, allowing them to enter cells much more efficiently than conventional delivery methods.
“Simple changes to the particle’s structure can dramatically change how well a cell takes it up,” Mirkin said. “The SNA architecture is recognized by almost all cell types, so cells actively take up the SNAs and rapidly internalize them.”
To evaluate their newly developed LNP-SNAs with CRISPR components, the researchers introduced them to multiple cell types — skin cells, white blood cells, human bone marrow stem cells, and kidney cells — and observed and measure various factors.
The team assessed how effectively cells absorbed the LNP-SNAs particles, whether these particles caused any toxic effects, how well they delivered the CRISPR components, and most importantly, if the CRISPR system successfully made the intended genetic modifications.
Upon observation, they found that their LNP-SNA approach entered cells up to three times more effectively than the standard lipid nanoparticle delivery system, was significantly less toxic to cells, enhanced gene-editing efficiency by threefold and improved the success rate of precise DNA repairs by more than 60% compared to current methods.
“CRISPR could change the whole field of medicine,” Mirkin said. “But how we design the delivery vehicle is just as important as the genetic tools themselves. By marrying two powerful biotechnologies — CRISPR and SNAs — we have created a strategy that could unlock CRISPR’s full therapeutic potential.”
Looking ahead, the researchers plan to further validate their LNP-SNA approach in multiple in vivo disease models and hope to adapt it for a range of systems and therapeutic applications. The University’s spin-out, Flashpoint Therapeutics, is commercializing the technology, aiming to move it towards clinical trials.
The study will be published September 5, 2025, in the Proceedings of the National Academy of Sciences.
