05 June 2012

DNA container for transporting miRNA

A gene switch was made from DNA origami

<url>Scientists from the Massachusetts Institute of Technology have developed a way to turn off individual genes in cells using RNA interference.

It involves the delivery of special RNA to cells using particles created on the principle of DNA origami technology. The work of Lee et al. Molecular self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery is published in the journal Nature Nanotechnology, its brief contents can be found on the institute's website (Researchers achieve RNA interference, in a lighter package).

To create a gene switch, scientists used several small interfering RNAs (siRNAs), which bind to certain matrix RNAs in the cell and lead to their degradation. The work of the gene encoding this matrix RNA stops because of this.

In order for small RNAs to enter the cell and not be destroyed before that in the bloodstream, they were packed into microscopic particles created on the principle of DNA origami. The particles had the shape of a tetrahedron, six faces of which were made of double-stranded DNA. Similarly, scientists collect various microscopic structures of various shapes from fragments of nucleic acids.

As an illustration of the method's capabilities, the researchers decided to deliver small RNAs to mouse tumor cells. To do this, anchor molecules of folic acid (vitamin B9) were attached to the tetrahedron of nucleic acids. They directed the particles to cancer cells, which absorb folate much more actively than normal ones. Scientists observed the targeted delivery of particles and noticed that their half-life in the bloodstream is significantly longer than that of the small RNAs themselves without packaging.

After the discovery of the RNA interference method in the late 1990s, scientists are trying to come up with an optimal way to deliver small RNAs to the cells of multicellular organisms. This could potentially help treat many diseases. In some animals, this can be done very simply – for example, in nematodes, it is enough to put a worm in a solution of the corresponding RNA to turn off the gene.

In mammals, liposomes or polymers are used to deliver RNA, the effectiveness of which is not always high. Particles created using DNA origami have the advantage that they are easy to design and they are all identical to each other (and not, like liposomes, a mixture of particles of different sizes). However, DNA containers may be less stable in the bloodstream due to the presence of DNA-cutting enzymes there, and it is also worse to enter the cell due to its own negative charge.

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