Gene therapy under control
The first technology of gene therapy management has been created
Sergey Kolenov, Hi-tech+
Researchers from the USA have discovered a mechanism that allows you to "jam" the genes embedded in the cell or, conversely, stimulate their activity. The discovery makes it possible to subtly manage gene therapy after implementation, up to its complete stop. The lack of such a safety system was one of the key factors that hindered the mass clinical use of gene therapy.
Gene therapy allows you to insert DNA sequences into the patient's cells that are necessary to fight various diseases. For example, this way you can compensate for the congenital absence of a particular gene.
However, the technique has one significant drawback. After the genes are delivered to the cell, it is no longer possible to regulate their work or turn them off. Without a "control lever", gene therapy cannot be considered truly safe.
The solution to this problem was proposed by specialists from the Scripps Research Institute, whose work is described by Eurek Alert. They created a technique for managing gene therapy based on hammerhead-type ribozymes. These RNA fragments have an unusual property: immediately after assembly, they cut themselves into two parts.
If a fragment encoding a similar ribozyme is inserted into a therapeutic gene, the RNA produced on its basis will be cut before the protein begins to be synthesized. This process can be slowed down with the help of morpholine oligonucleotides attached to the ribozyme. They will stop the splitting of RNA and allow you to create a protein based on it.
Thus, the combination of ribozymes with morpholine oligonucleotides can be used as a "switch" for the genes embedded in the cell. Moreover, changing the concentration of oligonucleotides will allow to regulate the intensity of gene therapy.
Experiments with mice injected with genes for increased erythropoietin production confirmed that the use of ribozymes really allows you to "turn off" gene therapy. In turn, a small dose of morpholine oligonucleotides cancels this effect and increases the expression of the target gene by several hundred times.
According to the authors, their technique is the only way that exists today to regulate the level of gene therapy. Given that morpholine oligonucleotides have already been approved by the FDA, this may accelerate the transfer of the new technology to humans.
Article by Zhong et al. A reversible RNA on-switch that controls gene expression of AAV-delivered therapeutics in vivo is published in the journal Nature Biotechnology – VM.
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