Delivery of scissors for DNA
An international team of researchers from Tufts University (USA) and the Chinese Academy of Sciences have upgraded the delivery mechanism of CRISPR/Cas9 gene editing tools in the liver. The scientists used biodegradable synthetic lipid nanoparticles that deliver editing tools to the cell. In experiments with human kidney cell cultures synthesizing green fluorescent protein, the damage efficiency of the corresponding gene reached 90%.
The CRISPR/Cas9 complex in the process of cutting the target DNA. Source: Visual Science and Skoltech.
The developed lipid nanoparticles encapsulate the informational RNA (mRNA) encoding Cas9 and indicating the RNA guide. As soon as the contents of the nanoparticles enter the cell, the production of the Cas9 protein starts according to the mRNA template. The peculiarity of nanoparticles for delivery consists in disulfide bonds between synthetic lipids. Inside the cell, the disulfide bond of nanoparticles is broken, the contents (editing tools) are quickly and efficiently released.
Lipids containing biodegradable bonds form a wall of nanoparticles encapsulating Cas9 mRNA and RNA guide. When they enter the cell in vitro or in vivo, the bonds are destroyed, the particles disintegrate, releasing the "baggage", and the translation of mRNA into the active enzyme for editing the CRISPR/Cas9 genome begins. Source: article in the journal Advanced Materials.
The researchers tested the new method on mice. They targeted CRISPR/Cas on the PCSK9 gene to lower the level of low-density lipoproteins (so-called bad cholesterol).
As a result, the expression of PCSK9 in the liver of mice decreased by 5 times compared to the control group.
The CRISPR/Cas9 gene editing system is a powerful and promising tool that reveals the functions of hundreds of genes. Currently, it is not used for therapeutic purposes for the treatment of various diseases due to a number of difficulties, including the safe delivery of components for editing inside the cell. The authors hope that their work will help overcome some technical obstacles and contribute to the process of introducing CRISPR/Cas into clinical practice.
Article by J. Liu et al. Fast and Efficient CRISPR/Cas9 Genome Editing In Vivo Enabled by Bioreducible Lipid and Messenger RNA Nanoparticles is published in the journal Advanced Materials.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Tofts Now: Novel nanoparticles deliver CRISPR gene editing tools into the cell with much higher efficiency.