Compulsion to commit suicide
The genetic editor for the first time "forced" cancer cells to suicide
Molecular biologists have successfully applied the CRISPR/Cas9 genomic editor for the first time to suppress the growth of cancer cells and turn on their suicide program, and used it to treat several mice from cancer, according to an article published in the journal Nature Methods (Liu et al., Directing cellular information flow via CRISPR signal conductors).
The CRISPR/Cas9 genomic editor, called the main scientific breakthrough of 2015, was created by American scientist Feng Zhang and a number of other molecular biologists about three years ago, and since then it has undergone several upgrades that allow scientists to use it to edit the genome with absolute accuracy.
One of the most promising ways to use CRISPR/Cas9, according to Zhiming Cai from Shenzhen University (China), is the possibility of using this editor to "fix" self-destruction systems in cancer cells, the breakdown of which is most often the cause of tumor formation and its uncontrolled reproduction.
Molecular "passport"
This idea is considered so promising by the Chinese government that back in July of this year, Chinese molecular biologists received permission to conduct similar experiments on volunteers with an incurable form of lung cancer, which scientists will try to destroy by reprogramming their immune cells.
Tsai and his colleagues took the first step towards realizing this task by successfully testing CRISPR/Cas9 in the fight against cancer in mice, turning it into a kind of "emergency button" that responds to intracellular or artificial chemical signals and forces the cell to perform certain actions, including killing itself.
This small change changes the essence of CRISPR/Cas9 – it turns this editor into a selective tool, in fact, into a programmable bio-computer that begins to edit DNA only when certain conditions are met, for example, the presence of special defective proteins in cancer cells or drug signaling molecules that are injected into the tumor by doctors.
Such a system works quite simply – instead of the usual "guide" RNAs containing information about the edited genes, special versions of these molecules are used in it, which block the work of the Cas9 protein, which performs all operations on the genome. At one of its ends there is a section to which a certain drug or protein molecule can join and unlock Cas9.
Combat DNA Editing
Moreover, such an approach allows not only to kill certain cells, as scientists explain, but also to create whole logical chains and a kind of "bio-computers" based on RNA, which will make independent decisions inside the body on how to treat a particular disease or what changes need to be carried out in the genome at the current time and under the current circumstances.
Having tested the operation of this system on cancer cell cultures in vitro, Tsai's group tried to use it for cancer treatment, setting it up in such a way that the editor turned on when NPM protein molecules appeared, signaling the onset of cancer in the bladder. When Cas9 was turned on, it activated the so-called "guardian proteins" p53 and p21, disabled or inactive in cancer cells. Both of these substances are responsible for triggering apoptosis, a cellular self-destruction program that turns on under normal conditions with fatal DNA damage.
Their artificial inclusion, as shown by experiments on mice into whose body scientists injected small fragments of tumors, led to the mass death of cancer cells and a sharp decrease in the size and mass of the tumor, but the work of CRISPR/Cas9 did not affect healthy cells in any way, where NPM molecules and other cancer markers are extremely rare or are not present in principle.
Such successes and the creation of a CRISPR/Cas9 "programming" system, as the authors of the article hope, will accelerate the development of anti-cancer genomic vaccines safe for clinical use and will help them pass tests on animals and volunteers faster.
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12.09.2016