Magnetized CRISPR
Magnetic nanoparticles delivered CRISPR precisely to the tumor
Daria Spasskaya, N+1
American bioengineers have developed an approach for targeted delivery of components of a genome editing system using a magnet. To do this, the DNA encoding the components of the CRISPR-Cas9 system was packed into insect virus particles coated with iron oxide nanoparticles. Such particles can be "turned on" in tissues using a directed magnetic field, and they are "turned off" with the participation of the host's immunity. Using magnetic CRISPR delivery, the authors managed to locally break a gene in a tumor in mice. The work was published in Nature Biomedical Engineering (Zhu et al., Spatial control of in vivo CRISPR–Cas9 genome editing via nanomagnets).
Any therapeutic approach that requires the local presence of a drug in a specific organ in an animal's body faces the problem of targeted delivery. If the therapeutic agent is DNA, this problem is solved, for example, by using adeno-associated viral vectors as "postmen", which, depending on the serotype, have affinity for different tissues and deliver DNA to cells. Nevertheless, such vectors have limitations on the size of the "parcel", besides, since they are constructed on the basis of mammalian viruses, their behavior in the body is not always predictable.
Researchers from Rice University proposed sending DNA-containing particles to the address using a magnetic field, pre-coating them with iron oxide nanoparticles. At the same time, the researchers chose vectors based on insect viruses (baculovirus vectors) as a means of delivery. They are not able to replicate in the mammalian body, however, they easily penetrate into many types of cells and provide temporary expression of the DNA parcel there. However, it used to make sense to introduce them only locally in the tissue, because with systemic delivery (for example, through blood), baculovirus particles are inactivated by the complement system in serum.
From left to right: magnetic nanoparticles, baculovirus particles, viral particles coated with nanomagnets. Drawings from an article in Nature Biomedical Engineering.
The authors of the work found that iron oxide-coated viral particles in the presence of a magnetic field effectively penetrate into cells, regardless of the complement system. Thus, in the absence of a field, the particles are inactive, and under the action of a magnet they begin to work and send DNA to cells.
In an experiment on mice, scientists delivered DNA encoding the CRISPR-Cas9 genome editing system, "charged" against the Vegfr2 gene encoding the vascular endothelial growth factor receptor. First, magnetic baculovirus particles with a "package" were injected into a subcutaneous tumor in mice, where DNA was effectively expressed under the action of a magnet, and CRISPR inactivated the desired gene. Then the researchers tested the effectiveness of editing with systemic delivery and showed that if the particles are injected intravenously, they end up in a "magnetized" place (liver or tumor) and allow the gene to be broken there with an average efficiency of several percent (per whole organ).
The scheme of the experiment on the targeted delivery of DNA particles to the liver.
Although this is not very much, such an approach would help to avoid the toxicity of the system associated with inappropriate editing in the body and the long-term presence of foreign DNA.
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