2009 Progress Report – Executive Summary
In the past year, the work of our Center has become focused on the construct that we call the functional protocell or, more frequently, just protocell.
How is the protocell like a biological cell? Like a biological cell, it is surrounded by a membrane that contains lipids and proteins. Like a biological cell, it contains a solution inside comprised of water and solutes, which may be ions or molecules. By varying the contents of the protocell interior, and by varying the chemical composition of the surface membrane, the protocell may acquire a great variety of properties, just as biological cells have various properties based on the same kind of variation.
How is a protocell different from a biological cell? For the protocells we make, there are two major ways; 1) it can not replicate itself, and 2) it can not change its shape.
Our protocells come in two major forms. One is the delivery protocell, which is designed to enter living cells and delivery stuff. The other is the honeypot protocell, which is designed to have some interesting interaction on its surface.
In the past year, scientists in our Center have been able to design delivery protocells to do some interesting things. They have made a protocell that will enter liver cancer cells but leave healthy liver cells alone. Not only will it enter the liver cancer cells but it will kill them, if it is loaded with the right drug. These experiments are in cell cultures, so we do not know how these will work in an animal, or ultimately a human. There are a lot of issues in animals that are not in cell culture. For example, the protocell might provoke a destructive immune response in the host animal. Actually we think we know how to prevent that, but this remains to be shown. Another issue is tissue specificity. We know that the protocells will not enter normal liver cells in culture, but might they enter some other nomal cell type. So many issues remain before our protocells can be enlisted to fight cancer, with confidence that they will do more good than harm. But we like to think those issues will be resolved.
Our honeypot protocells have shown interesting results against viruses in culture medium. We coat the surface of the protocell with a human receptor protein. In the human cell the virus uses this protein to gain entry. This protein on the surface of the protocell tricks the virus. The virus senses the human protein, thinks it has found a new cell home, and deploys a fusion protein to force its way into the cell interior. But it cannot get inside the protocell, because the interior of the protocell is silica, which is the scientific name for glass. Better yet, it appears that in trying to get into the protocell, the virus has somehow disabled its fusion protein, so when it leaves the protocell, it has lost the ability to get into human cells. As with the delivery protocell, we may be years from using a construct like this in human antiviral therapy, but we think what we are seeing this year is a promising start towards that.
While some of our scientists are working with the protocells, other members of our team are trying to understand the molecular details of how the protocells work---,and why some protocell designs don’t work. We are trying to get such a detailed understanding of the protocell-living cell interaction that we can design a protocell in a computer and know what it will do. That may in fact not be achievable, but working towards that goal teaches us lots of stuff, not only about protocells, but also about living cells.
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