SYNTHETIC BIOLOGY
Engineered E. coli scavenges ammonia in the gut Researchers continue to discover the key roles our gut bacteria can play in our health, but they can also engineer these microbes to diagnose and treat disease. The biotech company Synlogic has been engineering bacteria to treat diseases associated with the gut microbiome for a decade. In Science Translational Medicine last week (2019, DOI: 10.1126/scitranslmed. aau7975), company researchers describe a strain of Escherichia coli that can reverse dangerously high levels of ammonia in the blood. “The data shows we can engineer bacteria to carry out a specific function, deliver them to humans, and that they perform as designed,” says Paul Miller, Synlogic’s chief scientific officer. The human body mostly produces ammonia while metabolizing protein in the intestines, and the liver then turns it into
urea. Liver diseases and some genetic disorders can disrupt this process and cause ammonia to build up in the blood, with severe consequences due to ammonia’s toxicity. Current treatments for these conditions either try to reduce the activity of ammonia-producing bacteria in the gut or physically adsorb the ammonia once it is made. In the new approach, the Synlogic team modified E. coli Nissle 1917, which is sold as a probiotic under the name Mutaflor in Europe. The engineered bacteria, which are called SYNB1020 and can be taken as a pill, metabolize ammonia in the gut, turning it into the amino acid l-arginine. Tests showed that the engineered bug reduced ammonia levels and increased survival in mice with excess ammonia in their blood. In a Phase I clinical trial in
The engineered E. coli metabolizes excess ammonia in the gut that could otherwise cause serious complications in patients with liver disease. healthy people, SYNB1020 survived the passage through the digestive system but didn’t colonize the guts long term, another feature the researchers engineered into the bacteria. “It’s good to see real-world applications coming into practice,” says Pamela Silver, who works on gut microbiome engineering at Harvard University. “We are good at engineering bacteria and are getting better all the time. This is a rapidly growing area and the more successes, the better.” SYNB1020 is now in Phase Ib/IIa clinical trials.—LAURA HOWES
BIOTECHNOLOGY C R E D I T: SY N LO G I C/V E RGE S C I EN TI FI C CO M MUN I CAT I O N S /FA LCO N I E R I VI SUALS (E . CO L I ); U CS D (SCA F FO L D)
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Therapeutic bacterium passes Phase I trial
3-D printed implants heal spinal injuries Formfitting devices precisely bridge lesions in rats and help neurons regrow With the help of a 3-D printed hydrogel implant, researchers have demonstrated that they can restore leg movement in rats with severe spinal cord injuries (Nat. Med. 2019, DOI: 10.1038/s41591-018-0296-z). Using a fast, light-based printing technique, the team tailored the implants to precisely fit a cut or tear in a spinal cord, guiding nerve cells to grow across the injury site and reestablish neural connection. About 17,700 people in the US get spinal cord injuries every year. Surgery and therapy can restore some movement or sensation in affected parts of the body, but these injuries are usually permanent because damaged spinal nerves do not regenerate on their own. Surgically grafted polymer implants could coax and guide spinal nerves to reconnect, but these devices often are poor fits for randomly shaped spinal lesions. To make better-fitting implants, a team of researchers at the University of California San Diego, led by neuroscientists
This 2 mm thick, 3-D printed scaffold is made of polyethylene glycol and gelatin methacrylate with a design customized to fit a rat’s spinal cord lesion. Jacob Koffler and Mark H. Tuszynski and nanoengineer Shaochen Chen, used a 3-D printing method that relies on millions of microscopic mirrors to shine ultraviolet light in a defined pattern onto a solution of photocurable polymers. Based on the
pattern of the light reflected into the solution, the polymers solidify and form the desired 3-D shape, which matches a given lesion. To test the implants, the team split rats with severed spinal cords into three groups: one group received implants loaded with neural stem cells suspended in a cocktail of growth factor proteins, another got empty scaffolds, and the third received just stem cells. Six months later, animals with the cell-loaded implants were able to move their hind legs, while those in the other two groups could not. Michael C. McAlpine, a mechanical engineer at the University of Minnesota Twin Cities, says the printing method could be used with other implant designs. He is working on implants with cells directly printed into the scaffolds, which allows his team to place various types of cells exactly where they are needed for growth. The UCSD team is “focusing on anatomical accuracy,” he says. “In the future maybe the two approaches could be combined for even better results.”—PRA-
CHI PATEL, special to C&EN JANUARY 21, 2019 | CEN.ACS.ORG | C&EN
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