Molecular Bloodhounds
One of the main problems in the treatment of cancer and many other diseases is the difficulty of accurately targeting target cells and preserving all other cells at the same time, because they can differ only in subtle parameters.
A group of researchers from the University of Washington School of Medicine and the Fred Hutchinson Cancer Research Center in Seattle described the design of new nanoscale devices made of synthetic proteins. They deliver the therapeutic agent only to cells with certain, predetermined combinations of markers on the membrane surface.
It is noteworthy that these "molecular bloodhounds" work by themselves and can find the cells they were programmed to search for. The discovery will help solve a key problem in medicine: how to influence specific cells in a heterogeneous environment. Researchers have created a way to direct almost any biological function to any cell by changing combinations of cell membrane markers.
The devices are called Co-LOCKR, or orthogonal carrier proteins/keys (Colocation-dependent Latching Orthogonal Cage/Key pRoteins) that are fixed depending on colocalization. Each Co-LOCR consists of many synthetic proteins that, when separated, are inactive. But when the fragments connect on the surface of the target cell, they change shape, thereby activating a kind of molecular beacon.
An artistic illustration of the Co-LOCKR nanodevice, which is assembled from individual fragments only on the surface of those cells that have the desired combination of biomarkers on the surface. Source: Institute for Protein Design.
The presence of such beacons on the cell surface can direct a predetermined biological function, for example, destruction, to a specific target cell.
The researchers demonstrated that Co-LOCKR can focus the activity of CAR T cells to destroy cancer cells. In the laboratory, they mixed Co-LOCKR proteins, CAR T cells and a variety of potential target cells. There were one, two or three markers on the surface of the latter. T cells killed only cells with a given combination of markers. If the cell also had a pre-determined "health marker", then it did not attract lymphocytes.
It is known that T-cells are extremely effective killers, so the ability to direct their activity exclusively to cells with a certain combination of antigens will raise the effectiveness and safety of immunotherapy to a new level.
Unlike most other methods based on artificial cells, this strategy of targeting cells is completely dependent on proteins and works much faster.
The authors believe that Co-LOCKRS will be useful in many areas of medicine that require precise targeting of cells, including immunotherapy and gene therapy.
Article by M.J.Lajoie et al. Designed protein logic to target cells with precise combinations of surface antigens is published in the journal Science.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of UW Medicine: New 'molecular computers' find the right cells.