Targeted siRNA Silences Cancer Cells
Mark E. Davis, PhD
Another Cancer Treatment - Silencing RNA
Mark E. Davis, professor at California Institute of Technology, has been working on a new cancer treatment for specific types of malignancies. The treatment delivers what are called silencing RNA (siRNA) sequences to specific genes implicated in cancer growth and creation. This therapy, because it is still so new, can also be called RNA interference or RNAi.
Dr. Davis is no stranger to this branch of science. See my hub on "How Nanotechnology has been applied to cancer treatment." In that attempt, which is still undergoing clinical trials, Dr. Davis encapsulated a cancer toxin in a nano-particle consisting of a sugary starch called Cyclodextrin which is non-toxic and does not cause an immune response. Buried within the cyclodextrin is a toxic molecule called Camptothecin. Because cancer cells are "ravenous", delivering a toxin in a sugary coating to them this way appears to be quite effective. Again, trials are ongoing.
Dr. Davis' newest field of research is both preventative and curative in nature. This latest foray into oncological* science uses nanotechnology to deliver silencing RNA to DNA strands which may be capable of expressing (malignancies) cancers.
Cyclodextrin is still being used and since siRNA is non-toxic this new technique promises to be much easier on the patient that current chemo-therapies.
Self Organizing "Smart" Bombs
The current research in this area is self-formation of cyclodextrin molecules (again because they are non toxic, do not illicit an immune response, and are self organizing) in a variety of formations. Researchers have found that cyclodextrin nano-particles with specific size and geometric formation tend to "flock toward" specific areas of the body. The net effect is to tailor the nano-particle to a particular biological area such as the prostate, pancreas, or skin. This in turn will give a much finer degree of control over how the particles work, what they target, and how effectively they deliver the "payload." Payload in this case being a toxin strong enough to destroy cells...cancer cells.
Another "upside" to this delivery method is that it does not rely on (potentially mutating) viruses as a delivery vehicle and since siRNA is non-toxic typical side-effects of traditional chemo-therapy could be a thing of the past.
Targeting and Cell Uptake
To date all active delivery of these siRNA "bombs" have been preformed on mice. Because the nano-particles have been tailored as to size and shape they tend to deliver themselves to the appropriate places despite having been injected systemically*. Thus the reference to biological function above.
Another issue with this method is uptake. e.g. the ability of the drug, siRNA, or toxin to pass through the cell membrane of the offending cell. If uptake is inhibited the nano-particle may get to it's target, but the payload will never make it's way into the "offending" cell.This problem has also been successfully addressed (to date) with the formation of the self-organizing sugar molecules. Most cells, healthy or otherwise, run on sugars.
Another issue that had to be addressed was the very short "half-life" of siRNA moving freeling in a living body. Typically, siRNA have a very short life (seconds to minutes) and are also readily processed by the kidneys and expelled from the body. By encapsulating these agents within customized nano-particles the half-life of these agents is greatly expanded. They also bypass the renal system (kidneys) due to their size.
Of course all of this is necessary if the agents are to be injected into the body where all manner of organs and cells are designed to destroy "invaders."
* Systemic meaning that the drug is everywhere within the body...the system.
To date studies indicate that this delivery system works effectively in reducing or destroying prostate, pancreatic, and skin (melanoma) cancers in mice. Because these specific types of cells are targeted by the shape of the nano-particle, systemic (body wide) reactions are greatly reduced or even eliminated. And because the delivered "drug" is siRNA the risk of toxic side-effects if further reduced.
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