Lipid Nanoparticles Deliver CRISPR/Cas9 into Organs with High Efficiency

Researchers at Tufts University and the Chinese Academy of Sciences have developed a new lipid nanoparticle which can deliver CRISPR/Cas9 gene editing tools into organs with high efficiency, suggesting that the system is promising for clinical applications.

The CRISPR/Cas9 system is currently being investigated as a way to treat a variety of diseases with a genetic basis, including Duchenne muscular dystrophy, Huntington’s, and sickle cell disease. While the system has significant promise, there are some issues that need to be resolved before it can be used clinically. CRISPR/Cas9 is a large complex, and it is difficult to get it inside cell nuclei where it is needed for gene editing.

Scientists have tried a variety of delivery vehicles for CRISPR/Cas, which are intended to carry the gene editing tools to their location and help them enter the cell and nucleus. These have included viruses and various types of nanoparticle. However, to date, these have suffered from low efficiency, whereby very little of the delivered agent reaches the cells or organs where it is needed.

The team’s new nanoparticles consist of a synthetic lipid layer which is broken down once the nanoparticles enter a cell, releasing the contents of the particles. The particles include messenger RNA versions of the gene editing tools, which the targeted cell then translates into a protein by itself using its own cellular machinery, meaning that the bulky proteins do not need to be directly transported into the cell.

The nanoparticles demonstrated over 90% efficiency in affecting gene expression in treated kidney cells. When the researchers tested them in mice, they were able to significantly reduce the expression of a gene called PCSK9, which is linked to cardiovascular disease and levels of cholesterol, suggesting that the technique could be useful in humans.

“The lipid nanoparticles are one of the most efficient CRISPR/Cas9 carriers we have seen,” said Ming Wang, a researcher involved in the study. “We can actually knock down PCSK9 expression in mice with 80 percent efficiency in the liver, suggesting a real promise for therapeutic applications.”