Modified red blood cells for drug delivery
Researchers at the Whitehead Institute for Biomedical Research, using genetic and enzymatic modifications, have turned red blood cells into carriers suitable for spreading a wide range of compounds throughout the body, ranging from medicines and vaccines to imaging agents.
Erythrocytes are very attractive for use as a therapeutic carrier for a number of reasons. They are numerous, and their life span in the body reaches 120 days. Moreover, in the process of maturation, the precursors of red blood cells push out the nucleus along with the DNA contained in it. As a result, mature cells do not carry genetic material and, accordingly, no traces of genetic modifications potentially capable of causing tumor growth.
The authors modified the early precursors of erythrocytes using genes encoding altered cell surface proteins. As a result, maturing nuclear-free erythrocytes carried proteins on their surface, to which almost any compounds, including therapeutic small molecules and toxin-specific antibodies, can be attached with the help of the enzyme sortase A. The manipulations performed in this case do not harm either the cell or its surface.
To prove the viability of the developed approach, the researchers loaded modified mouse erythrocytes with biotin and injected them into animals. The life expectancy of such red blood cells in the bloodstream was 28 days.
In vitro experiments have also demonstrated the ability of antibody-loaded modified mouse erythrocytes to selectively interact with target cells.
Moreover, the authors have already conducted a series of experiments with human erythrocytes and have shown that these cells are also suitable for carrying out the manipulations described above.
They believe that the developed approach will find wide application in clinical practice. Modified erythrocytes can be used to remove "bad" cholesterol from the bloodstream, deliver blood clot-dissolving drugs to the areas of deep vein thrombosis and ischemic stroke, as well as for the treatment of chronic inflammatory processes using antibodies to proinflammatory signaling molecules. Two more areas currently being developed are their use as carriers of vaccines that neutralize toxins, as well as drugs that suppress immune reactions accompanying therapy with protein-based drugs.
Article by Jiahai Shi et al. Engineered red blood cells as carriers for systematic delivery of a wide array of functional samples is published in the journal Proceedings of the National Academy of Sciences.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the Whitehead Institute for Biomedical Research:
Engineered red blood cells could carry precious therapeutic cargo.
Portal "Eternal youth" http://vechnayamolodost.ru02.07.2014