Engineers Design Programmable RNA Vaccines
Tanya Trofimencoff posted on August 04, 2016 | 2698 views
Programmable RNA vaccines can be manufactured in just one week. (Image courtesy of MIT.)
Programmable RNA vaccines can be manufactured in just one week. (Image courtesy of MIT.)
With the Olympics starting soon, many are worried about the risk of spreading the Zika virus across the globe. Fortunately, our weapons against disease outbreaks are getting better all the time.

A team of MIT engineers recently developed a customizable vaccine, manufactured within just one week, that could be rapidly deployed in response to disease outbreaks. Preliminary vaccines were tested on mice against Ebola, H1N1 influenza and toxoplasma gondii (a relative of the parasite that causes malaria), and results were 100 percent effective.

The vaccine contains messenger RNA (mRNA), which can be designed to code for any viral, bacterial or parasitic protein. The mRNAs are packaged into a molecule that delivers the RNA into cells, where it is translated into proteins that trigger immune responses. The team’s ultimate goal is to use this approach to create cancer vaccines capable of teaching the immune system to recognize and destroy tumors.

“This nanoformulation approach allows us to make vaccines against new diseases in only seven days, allowing the potential to deal with sudden outbreaks or make rapid modifications,” said Daniel Anderson, associate professor in MIT’s department of chemical engineering.

Engineering Customizable Vaccines

Vaccines available today usually contain inactivated forms of viruses and require months to manufacture. Other vaccines contain proteins normally produced by infectious microbes, but immune responses are weak and typically require chemical support.

In contrast, RNA vaccines induce host cells to produce many copies of the proteins they encode. The result is a much stronger immune reaction.

To make RNA vaccines safe and effective, Omar Khan, postdoctoral follow at the Charles Koch Institute, packaged RNA vaccines into a nanoparticle made from a branched molecule known as a dendrimer. RNA is negatively charged and binds to the temporarily positively charged dendrimer.

Dendrimer structure. (Image courtesy of Biomedical Engineering, University of California, Irvine.)
Dendrimer structure. (Image courtesy of Biomedical Engineering, University of California, Irvine.)
The dendrimer-RNA structure is then folded over itself repeatedly to generate spherical vaccine particles with a diameter of 150 nanometers (similar to the size of many viruses). The RNA sequences are customizable, producing any protein desired, and they include instructions for amplification of the RNA to produce more protein. 

Injected into the muscle, RNA is translated into proteins that are then released to trigger the immune system response. In the study, T-cell and antibody responses were achieved.

During lab tests, mice received a single dose of one of the vaccines and showed no symptoms following exposure to the real pathogen—Ebola, H1N1 influenza or toxoplasma gondii. In addition, since RNA does not cause mutations, it is safer than DNA vaccines, which have the potential to infiltrate the host genome.

Guarding Against Disease Outbreaks

The rapid manufacturing time of the customizable vaccine may be especially effective to fight influenza; vaccines today require months to grow the virus inside chicken eggs. So the next time unexpected flu strains appear, such as with the 2009 pandemic-causing H1N1 virus, quickly produced vaccines could have a better chance of preventing outbreaks.

“This could not only be applicable to the bugs they talked about, but could also be applicable for something even more important, which is an unknown virus,” noted Joseph Rosen, professor of Surgery at the Dartmouth College Geisel School of Medicine, “In response to a pandemic, whether natural, accidental or intentional, they could produce a vaccine in a week.”

Leaders of the project, Khan and Jasdave Chahal, a postdoctoral fellow at MIT’s Whitehead Institute for Biomedical Research, plan to start a company to license and commercialize the technology.

In addition, they hope to create vaccines for Zika virus, Lyme disease and other cancer vaccines. For the latter, vaccines target genes turned on during embryonic development. Dormant in adulthood, these genes can become reactivated in a type of cancer known as non-small cell lung tumors. With quick processing speeds and delivery, the RNA vaccine may help put a stop to future outbreaks.

For a different approach to fighting disease outbreaks, read about real-time forecasting global epidemics.

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