RNA – Loaded Nanoparticles

The discovery of RNA interface, which won researchers, Andrew Fire and Craig Mello the 2006 Nobel Prize in Physiology or Medicine, has been used to create more effective treatments for diseases like cancer. RNA interface technology, also known as RNAi, can target human cells and “silence the target gene”. What this means is that the proteins created in cancerous cells, which are responsible for a myriad of activities within the cell, can be targeted and caused to go through degradation and thereby lead to a loss of that protein. Instead of attacking the protein itself however, which is difficult due its 3-D dimensions, the mRNA is targeted. These mRNA’s (messenger RNA) are responsible for carrying the genetic instructions from the DNA on how to create a given protein. When RNAi technology is applied, a targeted area of the mRNA can be sliced and inhibited from creating a certain protein. Without certain proteins, the treatments for cancer patients will become more effective.

A major problem with the application of the technology is how to get the therapeutic RNA into the cell. “When injected on their own, so-called small interfering RNAs (siRNAs) are quickly filtered out by the kidneys, and researchers have struggled to design particles that carry their contents to target cells with enough specificity, or that don't cause toxicity or elicit an immune reaction from the body.” Nevertheless, Mark Davis, the Warren and Katharine Schlinger Professor of Chemical Engineering at Caltech, and the research team’s leader, has already been studying ways in which deliver nucleic acids into cells. Davis and his team have created a “four-component system – featuring a unique polymer – that can self-assemble into a targeted siRNA-containing nanoparticle. Once the nanoparticle reaches its destination, the cancerous cell can then releases the siRNAs.

Using the new technique with the RNAi technology, the team was able to analyze tissue from trial participants. There have been several different studies and trails, all in experimental and early stages using RNAi. The three melanoma patients in the trail at Caltech have been given different dosages. A direct relationship between the amounts of particles in the tumor and the dosages was discovered; “That's the first time anyone has seen that for any kind of particle delivery system, whether it's a liposome, a nanoparticle, or anything," said David. Another exciting finding was that the mRNAs were cut in the exact same way the siRNAs were intended to cut. A different trail, funded by the Department of Science and Technology of Zhejiang Province and by City of Hope National Medical Center and Beckman Research Institute, was used in breast cancer patients. “The study demonstrated the potential of inhibiting telomerase[using siRNAs] as an effective treatment of breast cancer when used alone and, when used in conjunction to doxorubicin [most common drug used for breast cancer treatment], could potentiate the cytotoxic effect of the drug to breast cancer cells.”

The side affects of the patients have yet to be revealed, and although the scale of the trails are small, there is much hope for this new technology to allow more effective cancer treatments. ‘"At the very least, we've proven that the RNAi mechanism can be used in humans for therapy and that the targeted delivery of siRNA allows for systemic administration," Davis says. "It is a very exciting time."


Sources:

http://www.physorg.com/news188378267.html
http://www.technologyreview.com/biomedicine/24841/page2/
http://www.biomedcentral.com/1471-2407/9/133