Scientists at Northwestern University have developed a new way to deliver CRISPR gene-editing tools using nanostructures called lipid nanoparticle spherical nucleic acids (LNP-SNAs). These structures have a dense shell of DNA that protects the gene-editing machinery, including Cas9 enzymes, guide RNA, and a DNA repair template. In lab tests with human and animal cells, the LNP-SNAs entered cells up to three times better than traditional lipid particle delivery systems.
They also caused much less toxicity and improved gene-editing efficiency by three times. Precise DNA repair was enhanced by over 60% compared to existing methods. The study, published in the Proceedings of the National Academy of Sciences, shows how these nanostructures could help CRISPR be used more widely in genetic medicine.
The architecture of the nanomaterials, not just their composition, determines how well they work. “CRISPR is an incredibly powerful tool that could correct genetic defects, thereby decreasing disease susceptibility or even eliminating diseases outright,” said Dr. Chad A.
Mirkin, who led the study. “However, getting CRISPR into the right cells and tissues efficiently has been a challenge.
Crispr delivery enhanced with nanostructures
Using SNAs to deliver CRISPR components, we’ve maximized its efficiency and expanded the range of applicable cell and tissue types.”
Traditionally, viruses and lipid nanoparticles have been used to deliver CRISPR into cells. While viruses work well, they can cause immune responses and side effects. Lipid nanoparticles are safer but often get stuck in cellular compartments and fail to release their cargo.
Mirkin’s approach uses SNAs, which are spherical DNA and RNA structures that can protect CRISPR machinery and deliver it into cells without triggering immune responses. The SNAs interact with cell surface receptors, making it easier for them to enter cells. Their surface DNA can also be modified to target specific cell types.
The effectiveness of the LNP-SNAs was tested in various cell cultures, including skin cells, white blood cells, human bone marrow stem cells, and human kidney cells. The results showed significant improvements in particle uptake, reduced toxicity, and successful delivery and execution of gene edits. The next steps for Mirkin’s team include testing the system in various disease models in living organisms.
The modular nature of the platform means it could be used for a wide range of therapeutic applications. Northwestern’s biotechnology spin-out, Flashpoint Therapeutics, is leading the commercial development of this technology, with the goal of moving it into clinical trials quickly. “Combining the power of CRISPR and SNAs gives us a strategy that could fully realize CRISPR’s therapeutic potential,” Mirkin concluded.
