(228bw) Microbiome-Bots for the Treatment of Inborn Errors of Metabolism

Probiotic bacteria have been commercially sold as dietary supplements to treat or prevent various gastrointestinal disorders. Their inherent safety, abundance, and high-level of interaction with the hosts digestive tract coupled with recent advances to the genetic tools for manipulation have opened opportunities to exploit these organisms for unique therapeutic applications. We hypothesize that these bacteria can be genetically modified into â??microbiome-botsâ? capable of substituting catalytic function to the human digestive system to treat various inborn errors of metabolism in a safe and effective manner. This talk will primarily focus on our efforts in developing a lactic acid bacteria-based microbiome-bot that provides non-native metabolic function through delivery of engineered enzymes for treating galactosemia. Galactosemia is the general description for a group of rare autosomal recessive metabolic disorders that results from the improper folding of one of three enzymes involved in galactose metabolism. In all cases incomplete metabolism of galactose generates an accumulation of a toxic metabolite. Pathologies related to this disorder include permanent damage to major organs such as the liver, kidneys, brain, and ovaries. There are no current therapies approved for the treatment of galactosemia to date. The microbiome-bot platform provides a targeted solution for disorders arising within the human digestive tract. We also describe our efforts in expanding this technology beyond galactosemia to other inborn errors of metabolism for which there are currently few treatment options.