New nanoparticles provide CRISPR gene editing tools in cell with much higher efficiency

According to a recent study published in the journal, a research collaboration between Tufts University and the Chinese Academy of Sciences has resulted in a significantly improved release mechanism for the CRISPR / Cas9 gene editing method. liver. Advanced Materials. The delivery uses synthetic biodegradable lipid nanoparticles that carry the molecular modification tools in the cell to accurately modify the genetic code of cells with up to 90% efficiency. According to researchers, nanoparticles are one of the most effective CRISPR / Cas9 delivery tools reported to date. They could help overcome the technical barriers that allow genetic modification in a wide range of clinical therapeutic applications.

The CRISPR / Cas9 gene editing system has become a powerful research tool for discovering the function of hundreds of genes. He is currently studying as a therapeutic tool for the treatment of various diseases. However, there are still some technical hurdles to overcome before it can be practical for clinical applications. CRISPR / Cas9 is a large molecular complex containing both a nuclease (Cas9) capable of cutting across both strands of a targeted genomic sequence, and a modified "single-guide" RNA (sgRNA) that analyzes the genome to help the nuclease to find specific sequence to edit. As this is a large molecular complex, it is difficult to bring CRISPR / Cas9 directly into the nucleus of the cell, where it can perform its work. Others have incorporated editing molecules into viruses, polymers and different types of nanoparticles to insert them into the nucleus, but the low transfer efficiency has limited their use and potency for clinical applications.

The lipid nanoparticles described in the study encapsulate the messenger RNA (mRNA) encoding Cas9. Once the content of nanoparticles, including sGARN, is released into the cell. The cell's protein production machinery takes over and creates Cas9 from the mRNA template, thus completing the gene editing kit. A unique feature of the nanoparticles is synthetic lipids including disulfide bonds in the fatty chain. When the particles enter the cell, the environment within the cell opens the disulfide bond to disassemble the nanoparticles and the contents are quickly and efficiently released into the cell.

"We are just beginning to attend clinical trials on CRISPR therapies in humans," said Qiaobing Xu, co-correspondent author of the study and an associate professor of biomedical engineering at the University. Tufts. "There are many diseases for which CRISPR therapies could offer new hope – for example sickle cell disease, Duchenne muscular dystrophy, Huntington's disease and even many cancers." We hope this advance will allow us to progress CRISPR an approach effective and practical treatment. "

The researchers applied the new method to mice in an attempt to reduce the presence of a gene encoding PCSK9, the loss of which is associated with lower LDL cholesterol and a reduced risk of cardiovascular disease. "Lipid nanoparticles are one of the most efficient CRISPR / Cas9 transporters we have seen," said Ming Wang, also a co-correspondent of the study and a professor at the Chinese Academy of Sciences. from the National Molecular Sciences Laboratory in Beijing. "We can actually suppress the expression of PCSK9 in mice with 80% efficiency in the liver, which bodes well for a real promise for therapeutic applications."