Fighting Infection from the Inside
Infection and disease are among the greatest killers in human history. Millions of lives are lost worldwide every year due to sickness or a decline in health. Health and medical science have made great strides to combat the causes for these deaths, but the fight is far from over. While the treatments for some illnesses seek to implement methods, equipment, and bacteria not native to the body, inciting the body’s auto-immune system to take care of itself using its internal defense mechanisms can also be an effective solution.
Immune to the Immune System
Even without intervention, the human body’s immune system displays extraordinary capabilities, such as creating cells specifically designed to fight foreign agents that might cause it harm. However, while the body’s auto-immune system can be effective in fighting an infection, it does not always know when to fight. Certain diseases and viral infections can prevent the body from producing the response required to elicit a reaction from its internal defense mechanisms, thereby allowing the infected cells to thrive.
In some cases, when a cell becomes compromised by infection or a normal cell becomes cancerous, the body detects the abnormality and generates what is called a STING (stimulator of interferon genes) signal, which in turn produces type-1 interferons to stimulate our immune cells. These cells are a major part of our auto-immune system and are charged with removing the infected cells from our bodies. However, cells occasionally do not produce the level of STING signal necessary to elicit this reaction depending on the type of disease or infection. As a result, the body fails to detect a problem.
The Lock and Key
Many cells in our body exhibit a mechanism that can be described as a sort of “lock”, which is a STING receptor protein in the cytosol of the cell. This “lock” can then be activated by a “key”, which is a cyclic GMP-AMP (cGAMP) nucleotide. Working in tandem, the lock protein will stimulate the activation of the STING pathway once it comes into contact with the cGAMP. As such, a working lock and key are both needed to attract immune cells. Consequently, if either the cGAMP is unavailable in the vicinity or the STING receptor is missing from the cell, the STING signal is never emitted, and the infection can continue to propagate. Both parks of this lock-and-key combination are essential to triggering a response from the body’s defense mechanisms: the cGAMP lets the cell know there is a problem, and the STING receptor protein relays that message to the auto-immune system.
Northeastern Professor Jiahe Li has developed a delivery system that provides a solution to the problem of the missing lock-and-key. Li’s delivery system comprises two components: a cGAMP molecule and a STING receptor protein. These components are combined into a cohesive unit and introduced directly to the affected cells. Upon making contact with the cells, the STING receptor protein binds to the cell and uses the attached cGAMP key to cause the cell to emit a STING signal. In turn, the interferon-stimulated immune cells can find the afflicted cells and begin taking care of the problem internally.
For example, diseases such as cancer exhibit a feature that eliminates the STING receptor protein in the tumor cell’s membrane. These kinds of cells are very good at masking themselves from the mechanisms in the body’s immune system, allowing them to go undetected for long periods of time. This ability to hide from the body’s auto-immune response contributes to cancer’s deadly nature. However, with Li’s combination cGAMP and STING receptor protein, these cells can be given the ability to communicate with a cGAMP molecule by providing a STING receptor protein that can elicit a reaction from the infected cell. The body can then begin addressing the cancerous cells of its own accord.
The Platform’s Potential
Li’s delivery system is not specific to the cGAMP and STING protein, though. This method of introducing a combination of molecules in a cohesive fashion can be extended to other analog keys, as it is more of a platform for delivery than a specific combination of molecules. Li’s lock-and-key delivery system may lend a solution to other problems where a cell requires two or more components to stimulate a reaction, providing the potential to deliver more than just cGAMP and STING protein receptors.
Written by Joseph Burns
Want to learn about additional Northeastern technologies? Try these:
Interested in licensing tech? Email Mark Saulich, Associate Director of Commercialization.