Tumor Cell Targeting with a Little Help from siRNA

SiRNA, also known as interference RNA, is a class of double-stranded RNA molecules that has only recently been discovered and explored in depth. The main focus for much of siRNA research has been to suppress gene expression, therefore addressing the root problem for many chronic diseases directly. A recent application for this breakthrough technology has been cancer treatment and tumor cell targeting, which MIT’s Technology Review writes about HERE.
According to the article, tumor cells posses the ability to become very resistant to any cancer-destroying drugs by significantly decreasing the effectiveness of the chemotherapy process. The cells do this by undergoing mutations that do two things: they help reduce drug binding to the target cell’s membrane, and they create efflux pumps that reroute drugs directly out of the cell. The latter is accomplished by producing large amounts of P-glycoprotein that constitutes the pumps and therefore redirect the drugs without ever affecting the cell.
In order to combat the resistance, a biotech firm called EnGeneIC took bacteria cells called “minicells” that had been emptied of their DNA and replaced it with strands of siRNA, which was designed specifically to silence the gene responsible for the efflux pumps. By injecting a double strand (dsRNA), it attaches to an enzyme called a dicer which then cleaves the dsRNA into smaller pieces of siRNA. Next, the siRNA duplex attaches to another protein complex called a RISC. After unwinding, the activated RISC pairs the siRNA with the target mRNA where it is then cleaved and the protein synthesis is prevented, thus silencing the gene.
In this case the target was the P-glycoprotein gene which was responsible for producing the pumps. In addition to blocking the gene, researchers attached antibodies to the surfaces of the bacterial minicells that allowed them to adhere to markers on the tumor cells specifically and kill them. After injecting minicells intravenously into mice with aggressive forms of cancer, the study found that the mice with the minicell chemotherapy lived much longer than the control group with only standard intravenous infusion.
The advantage of siRNA treatment, as cited in the article, is that when combined with cells and target markers it possesses the ability to provide a focused attack on cells that are typically resistant to drugs. The opportunities and applications for a targeted attack are immense since drug resistance ranges from chronic disease progression to bacterial infections. However, the problem lies in the ever-increasing costs for personalized therapy. With every person containing their own distinct phenotype and gene variations, siRNA treatments must be tailor made on an individual basis, thus adding time and money. And while the article expressed that no side effects were experienced by the mice using the minicell treatment, more efficacy testing is currently underway on 96 primates, which could yield different results.
I believe the techniques expressed have a lot of potential and power, although the cost and technical factors still need to be worked out in order for a successful implementation of this therapy into our healthcare system. With appropriate communication between healthcare policy makers, physicians, and researchers, a system could be implemented that could regulate pricing per individual and cut some administrative costs. If this is achieved, it could be cheaper and much more effective to treat on an individual basis because patients would not only get healthier, but stay healthy.