SynBioFromLeukipposInstitute

Kevin Kit Parker wants to build a human heart. His young daughter loves the New England Aquarium in Boston. In this Science report, father’s and daughter’s obsessions have combined in an unlikely creation: a nickel-sized artificial stingray whose swimming is guided by light and powered by rat heart muscle cells. 

Incorporating advances in engineering, cell culture, genetics, and biomechanics, the “living” robot is “clearly a technical tour de force,” says Adam Summers, an integrative biologist at the University of Washington, Seattle. And some think that by melding cells and artificial materials into a pulsating structure, the device brings Parker’s dream of engineering a human heart a step closer. “One can imagine that one day we can use this technology to rebuild parts of the human body,” says Kedi Xu, a neural engineer at Zhejiang University in Hangzhou, China.

Recently I got to volunteer again at a “Building with Biology” event at the Museum of Science in Boston. Last year was the first event of its kind and now the program is spreading all over the country. The Building with Biology project has developed new resources and activities to engage and inform the public on synthetic biology. The NSF funded project is ramping up to include 200 sites nationwide that will each bring together scientists and the public to talk and learn from each other about synthetic biology. Last summer 8 museums held pilot events to test out the kits and guide the development of outreach resources.

MIT engineers have developed a new type of easily customizable vaccine that can be manufactured in one week, allowing it to be rapidly deployed in response to disease outbreaks. So far, they have designed vaccines against Ebola, H1N1 influenza, and Toxoplasma gondii (a relative of the parasite that causes malaria), which were 100 percent effective in tests in mice.
The vaccine consists of strands of genetic material known as messenger RNA, which can be designed to code for any viral, bacterial, or parasitic protein. These molecules are then packaged into a molecule that delivers the RNA into cells, where it is translated into proteins that provoke an immune response from the host.
In addition to targeting infectious diseases, the researchers are using this approach to create cancer vaccines that would teach 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 and improvements,” says Daniel Anderson, an associate professor in MIT’s Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES).
Anderson is the senior author of a paper describing the new vaccines in the Proceedings of the National Academy of Sciences the week of July 4. The project was led by Jasdave Chahal, a postdoc at MIT’s Whitehead Institute for Biomedical Research, and Omar Khan, a postdoc at the Koch Institute; both are the first authors of the paper.
Customizable vaccines
Most traditional vaccines consist of an inactivated form of a virus or other pathogen. These vaccines usually take a long time to manufacture, and for some diseases they are too risky. Other vaccines consist of proteins normally produced by the microbe, but these don’t always induce a strong immune response, requiring researchers to seek an adjuvant (a chemical that enhances the response).
RNA vaccines are appealing because they induce host cells to produce many copies of the proteins they encode, which provokes a stronger immune reaction than if the proteins were given on their own. The idea of using messenger RNA molecules as vaccines has been around for about 30 years, but one of the major obstacles has been finding a safe and effective way to deliver them.
Khan decided to package RNA vaccines into a nanoparticle made from a branched molecule known as a dendrimer. One key advantage of this material is that the researchers can give it a temporary positive charge, which allows it to form close associations with RNA, which is negatively charged. Khan can also control the size and pattern of the final structure. By inducing the dendrimer-RNA structure to fold over itself many times, Khan generated spherical vaccine particles with a diameter of about 150 nanometers. That makes them of similar size as many viruses, enabling the particles to enter cells by exploiting the same surface proteins that viruses use for this purpose.
By customizing the RNA sequences, the researchers can design vaccines that produce nearly any protein they want. The RNA molecules also include instructions for amplification of the RNA, so that the cell will produce even more of the protein.
The vaccine is designed to be delivered by intramuscular injection, making it easy to administer. Once the particles get into cells, the RNA is translated into proteins that are released and stimulate the immune system. Significantly, the vaccines were able to stimulate both arms of the immune system — a T cell response and an antibody response.
In tests in mice, animals that received a single dose of one of the vaccines showed no symptoms following exposure to the real pathogen — Ebola, H1N1 influenza, or Toxoplasma gondii.
“No matter what antigen we picked, we were able to drive the full antibody and T cell responses,” Khan says.
The researchers also believe that their vaccines would be safer than DNA vaccines, another alternative that scientists are pursuing, because unlike DNA, RNA cannot be integrated into the host genome and cause mutations.
“The option of rapidly creating a completely synthetic formulation that can be effective as a vaccine is an important addition to currently available vaccine strategies,” says Hidde Ploegh, an MIT professor of biology, a member of the Whitehead Institute, and an author of the paper, who added that it will be important to assess safety and cost.
Rapid deployment
The ability to rapidly design and manufacture these vaccines could be especially beneficial for fighting influenza, because the most common flu vaccine manufacturing method, which requires the viruses to be grown inside chicken eggs, takes months. This means that when an unexpected flu strain appears, such as the 2009 pandemic-causing H1N1 virus, there is no way to rapidly produce a vaccine against it.
“Typically a vaccine becomes available long after the outbreak is over,” Chahal says. “We think we can become interventional over the course of a real outbreak.”
Joseph Rosen, a professor of surgery at Dartmouth College’s Geisel School of Medicine and adjunct professor of engineering at Dartmouth’s Thayer School of Engineering, describes the new approach to vaccine development as “revolutionary,” because it could dramatically reduce the amount of time needed to respond to disease outbreak.
“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,” says Rosen, who was not involved in the research. “In response to a pandemic, whether natural, accidental, or intentional, they could produce a vaccine in a week.”
Khan and Chahal plan to start a company to license and commercialize the technology. In addition to the vaccines they have already designed, they hope to create vaccines for Zika virus and Lyme disease.
They are also working on cancer vaccines. At a recent “Mission: Possible” competition hosted by the Koch Institute, Khan and Chahal were part of a team that ended up withdrawing from the competition because an outside funder, the Advanced Medical Research Foundation, offered to support them.
For that project, the researchers designed vaccines that target genes that are normally turned on only during embryonic development. These genes, dormant in adults, often become reactivated in a type of cancer known as non-small cell lung tumors.
“We are all excited about the potential of this new approach to provide a new way of vaccine delivery,” says Robert Langer, the David H. Koch Institute Professor at MIT and an author of the paper.
Other authors of the paper include Whitehead Institute researchers Justine McPartlan, Lucas Tilley, Saima Sidik, and Sebastian Lourido; Koch Institute technical assistant Jonathan Tsosie; and U.S. Army Medical Research Institute of Infectious Diseases researchers Christopher Cooper and Sina Bavari.
The research was funded by the Department of Defense Office of Congressionally Directed Medical Research’s Joint Warfighter Medical Research Program, MediVector Inc., the Ragon Institute of MGH, MIT, and Harvard, and the Defense Threat Reduction Agency/Joint Science and Technology Office program in vaccines and pre-treatments.

MIT researchers have developed synthetic biological circuits (from bacteria, for example, as shown here) that combine analog and digital computation as living

The advent of second generation chimeric antigen receptors and the CD19 paradigm have ushered a new therapeutic modality in oncology. In contrast to earlier forms of adoptive cell therapy, which were based on the isolation and expansion of naturally occurring T cells, CAR therapy is based on the design and manufacture of engineered T cells with optimized properties. A new armamentarium, comprising not only CARs but also chimeric costimulatory receptors, chimeric cytokine receptors, inhibitory receptors and synthetic Notch receptors, expressed in naïve, central memory or stem cell-like memory T cells, is being developed for clinical use in a wide range of cancers. Immunological principles are thus finding a new purpose thanks to advances in genetic engineering, synthetic biology and cell manufacturing sciences.

Materials, energy and just about everything around us is finite. A more thorough understanding of the Earth’s limitations and commodity price volatility has made this a critical realisation for 21st century economies.

Still, conserving natural resources, while still enabling economic, environmental and social prosperity presents a significant challenge, especially in a context of increasing demands for “things”, in particular from the 3 billion new middle class consumers predicted to hit the global markets before 2050.

An emerging discipline may have at least part of the answer – want more “stuff”? Grow it!

Using micro-organisms, like yeasts and bacteria, modifying their DNA to turn them into microscopic factories, chemists and biologists are now able to grow a huge range of resources, from real cow’s milk to high-performance silk fibres.

A few years ago, Michael Levin faced a conundrum. He and his colleagues at the Tufts Center for Regenerative and Developmental Biology just outside Boston wanted to find a model that would explain why the flatworm—a model organism used throughout biology—looks the way it does. At a fundamental level, they wanted to be able to describe the cascade of events that leads to the growth of a head in one place and a tail in the other.

In fact, it was almost the same problem that Thomas Hunt Morgan, a Nobel Prize-winning evolutionary biologist and one of the founders of the modern study of genetics, faced more than a century ago. Back then, he was busying himself making careful cuts into flatworms. He sliced them lengthwise. He dissected them in half. From each segment, the worm grew a complete body. Eventually, Morgan carved off 1/279th of the worm, a bit selected from its mid-section, and demonstrated that it could regenerate an entirely new animal. He was trying, unsuccessfully, to understand why and how certain body parts developed where they did: Why did a head appear at one end of the worm after a cut?