A New Tool of Synthetic Biology: Synthetic Organelles
Mapping Prokaryotic Biodiversity into Eukaryotes Holds Limitless Possibilities
We are in the midst of explosive advancements in the life sciences that are poised to disrupt a broad range of industries (manufacturing, biopharma, food, agriculture, textiles, energy, data storage, etc.). The development of genetic engineering tools in the 1970s led to innovations that impacted these industries, and this next wave will be even more far-reaching, disruptive, and impactful.
Recent developments in genetic tools, molecular understanding, computational power have created a confluence of innovations that will impact the lives of everyone on the planet. While these genetic tools are powerful, they are also limited. Presently, we can only manipulate or insert a few genes per cell. Complex properties, such as photosynthesis (the use of light to make food in plants), energy generation in muscle cells, or making magnets that some animals use for navigation require hundreds of genes and are not reproducible by scientists using these genetic tools.
Plants and animals (a form of life with a type of cell called “eukaryotes”) deal with complex properties using compartments called organelles that specialize in a task. For example, the nucleus houses and reads genetic information, the mitochondria create energy, and chloroplasts undertake photosynthesis — in all, there are hundreds of known organelles. Much as a house is divided into rooms with specific uses, the eukaryotic cell is divided into organelles allowing functional specialization. From the discovery of the organelle over a century ago, scientists have dreamt of creating new or synthetic organelles. The first report of cross-species organelle transfer occurred in 1974. Scientists took chloroplasts from plant cells and transferred them to animal cells and they remained functional for a few weeks. Interestingly, the same year writer Len Wein created the comic book hero The Swamp Thing with exactly that origin story!
Returning from science fiction to fact (which is what entrepreneurs do!), nature created some organelles by using another form of life known as the “prokaryotes” as a building block. Prokaryotes use a simpler and smaller type of cell than the eukaryotes that do not have organelles. These are the bacteria and they are capable of an astounding range of properties (called biodiversity), such as living without oxygen or thriving at crazy high temperatures, or surviving space travel. When a eukaryote swallowed a prokaryote but did not digest it, the eukaryote gained a new function. When one prokaryote swallowed another but didn’t digest it, the “predator” gained a new function. The prokaryote got a nice safe new home and food so the two formed a type of biological marriage living together from then on. This is how plants gained the ability to do photosynthesis; the chloroplast evolved from swallowing photosynthetic prokaryotes; same with the mitochondria, which are present in every human cell. This was the inspiration behind Bell Biosystems, Inc. that we founded in 2009.
A new approach in medicine is to use eukaryotic cells as a drug to cure the disease rather than using a chemical to treat the symptoms. One of the big challenges in realizing these “cell therapies” is that it is really hard to figure out where the cells go after they are injected into the patient. Cell therapy is not likely to work if the cells go to the wrong place and, even worse, could cause more problems. This is the issue we wanted to solve and our idea was to create a synthetic organelle that would make cells magnetic so they show up in MRI, one of the safest medical imaging methods. Our innovation was the magnetic organelle or Magnelle®. Nature had even provided us the building block to use in a prokaryote called the magnetotactic bacteria. These ancient bacteria live deep in bodies of water all over the planet and use the earth’s magnetic field for navigation. They are perhaps the oldest compass, and we postulated that these cell therapies could navigate the human body. And luckily for us, magnetotactic bacteria were closely related to the ancestors of the chloroplast and mitochondria. All we needed to do was replicate tens of thousands of years of evolution in the lab. In 2020, scientists at the University of Michigan published a study using Magnelles to track a cell therapy they were developing for Alzheimer’s disease in a non-human primate showing that our Magnelles worked and were non-toxic.
Nature uses both genes and organelles for novel function, but to our knowledge, Magnelles are the only commercialized example of a synthetic organelle. However, many others are working on various incarnations and with the immense biodiversity of prokaryotes the possibilities are limitless. Imagine photosynthetic animals, plants that do not need fertilizer or can live on other planets, cells that make their own drugs — these are not yet on the market, but they are not science fiction either.
Prime Movers Lab invests in breakthrough scientific startups founded by Prime Movers, the inventors who transform billions of lives. We invest in companies reinventing energy, transportation, infrastructure, manufacturing, human augmentation, and agriculture.
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