Three in one
Yale scientists have developed a modular approach to the construction of immune cells
Dmitry Mazalev, Naked Science
The main advantage of this approach, called AAV – Cpf1 KIKO, scientists call the possibility of simultaneous introduction of several genetic modifications, which will increase the body's ability to resist cancer and other diseases.
Figure from the press release of Yale researchers develop modular approach to engineering immune cells – VM.
Researchers from Yale University (USA) have developed a new way of effective genetic engineering of immune cells, thereby increasing the body's ability to resist cancer and other diseases. A number of new life-saving treatments rely on the reconfiguration of human immune cells as live drugs in the body: for example, CAR-T therapy is based on genetically modified T cells – a type of immune cells of the patient. The results of the study are published in the journal Nature Methods (Dai et al., One-step generation of modular CAR-T cells with AAV–Cpf1).
The pre-existing reengineering process was inconvenient and inefficient. This led to the fact that a team of scientists led by Sidi Chen, associate professor of the Department of Genetics and the Institute of Systems Biology, used a system based on a cell's own repair mechanism to integrate new genes into its genome.
Experts used a protein capable of cutting sections of the genome at several points, and an adenoassociated virus to inject modified genes into certain places. The main advantage of this approach, scientists call the possibility of simultaneous introduction of several genetic modifications.
"Cancer cells are able to evolve and secrete a marker that we design for T cells to target. That's why it was important for us to get such T cells that can target more than one cancer marker," Chen explains.
T cells are often called the "infantry" of the immune system: they patrol the body in search of pathogen-infected or aberrant (deviating from the normal structure or condition) cells that can potentially lead to the appearance of a tumor. When T cells find their target, they multiply and go into "combat mode" to fight the threat.
With this new method of T-cell engineering, specialists can use multiple viral vectors to create more complex CAR-T cells that can simultaneously target multiple cancer markers. According to Chen, further development and research in this area will allow us to gain more knowledge about those genes that increase the proliferation of T cells, their ability to destroy cancer and increase their resistance. All this, according to the authors in their article, will help to make new methods of treatment more reliable and less toxic to the patient's body.
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