Good news! Fascinating stuff! Interesting approach to treat cancer!
"... Over the past decade, researchers have explored the reduction of toxicities from live bacteria by genetically deleting the parts of the bacterium that can cause toxicity; but this can lead to unwanted mutations in the bacterium itself and may substantially decrease therapeutic efficacy.
A team of engineers ... has now determined an effective approach to enhance the delivery of living engineered bacteria into cells, while maintaining the bacterium’s integrity and minimizing toxicity. ... the researchers describe a way of coating engineered bacteria with an inducible capsular polysaccharide (iCAP) that responds in a smart manner when delivered into the body.
Capsular polysaccharide (CAP) is a layer of water molecules that coats the surface of natural bacteria and acts as a shield against foreign infections. By converting CAP into iCAP, the researchers could apply programmable external stimulus that enables the engineered bacteria to evade immune attack, survive for a considerable duration in the host environment and deliver a tolerable therapeutic dose. ..."
A team of engineers ... has now determined an effective approach to enhance the delivery of living engineered bacteria into cells, while maintaining the bacterium’s integrity and minimizing toxicity. ... the researchers describe a way of coating engineered bacteria with an inducible capsular polysaccharide (iCAP) that responds in a smart manner when delivered into the body.
Capsular polysaccharide (CAP) is a layer of water molecules that coats the surface of natural bacteria and acts as a shield against foreign infections. By converting CAP into iCAP, the researchers could apply programmable external stimulus that enables the engineered bacteria to evade immune attack, survive for a considerable duration in the host environment and deliver a tolerable therapeutic dose. ..."
From the abstract:
"Living bacteria therapies have been proposed as an alternative approach to treating a broad array of cancers. In this study, we developed a genetically encoded microbial encapsulation system with tunable and dynamic expression of surface capsular polysaccharides that enhances systemic delivery. Based on a small RNA screen of capsular biosynthesis pathways, we constructed inducible synthetic gene circuits that regulate bacterial encapsulation in Escherichia coli Nissle 1917. These bacteria are capable of temporarily evading immune attack, whereas subsequent loss of encapsulation results in effective clearance in vivo. This dynamic delivery strategy enabled a ten-fold increase in maximum tolerated dose of bacteria and improved anti-tumor efficacy in murine models of cancer. Furthermore, in situ encapsulation increased the fraction of microbial translocation among mouse tumors, leading to efficacy in distal tumors. The programmable encapsulation system promises to enhance the therapeutic utility of living engineered bacteria for cancer."
"a, We engineered the biosynthetic pathway of bacterial CAP for tunable and dynamic surface modulation of the probiotic E. coli Nissle 1917 with synthetic gene circuits. This approach enables increased CAP levels upon induction to control immune evasion and clearance. b, The programmable CAP system enhances systemic delivery of bacteria by transiently expressing CAP. Non-CAP bacteria (thin gray cells) elicit toxicity by exposing the immunogenic bacterial surface, and permanently CAP-expressing bacteria (thick black cells) lead to overgrowth. The iCAP (blue cells) system enables transient encapsulation of bacteria, thus reducing initial inflammation while effectively clearing bacteria over time. c, The CAP system controls bacterial translocation among tumors. The iCAP system allows in situ activation of CAP in one tumor, which results in inducible bacteria translocation to distal, uncolonized tumors."
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