Inflammatory Bowel Disease (IBD) is a group of disorders affecting over 5 million globally, with Ulcerative Colitis (UC) and Crohn’s Disease (CD) being the most common types. Both UC and CD are characterised by chronic intestinal inflammation leading to long term discomfort and disability. IBD often develops in early adulthood and significantly affects quality of life.
Currently available drugs to treat IBD are largely non-specific to the area requiring treatment, resulting in serious side effects. Moreover, many are injectable and can only be administered in hospitals.
CHAIN’s novel treatment will be targeted to the gut and taken orally at the patient’s convenience. It will be significantly cheaper than existing drug options. The treatment is suitable for long term use and may also be used alongside current treatments to reduce relapse and the need for steroids or immunosuppressants.
CHAIN’s live biotherapeutic product delivers Butyrate and other bioactives to the colon and is a promising new treatment for IBD and Colorectal Cancer. CHAIN has demonstrated efficacy using intestinal organoids developed using endoderm stem cell biology.
Butyrate is produced in a healthy gut if dietary fibre is consumed and the healthy gut bacteria that ferment this fibre to produce butyrate are present. Butyrate is the major source of energy for cells in the human gut and reduces inflammation.
Clostridium can also be engineered to produce stereospecific high value chemicals for the fine chemical industry. Conventional chemical synthesis can be difficult, inefficient and costly requiring expensive chiral catalysts, solvents, harsh physical conditions and results in unwanted by-products making purification difficult. In contrast, fermentation or enzymes are highly stereospecific and can be performed under mild reaction conditions using more sustainable feedstocks.
For example, (R)-1,3 butanediol is a key building block for pheromones, fragrances, insecticides and a key intermediate for the synthesis of penem and carbapenem β-lactam antibiotics. We are currently looking for partners interested in co-developing our Chiral Switch™ technology for this particular product and product related applications.
- Modular thus facilitating the combinatorial construction of Clostridium–E. coli shuttle plasmids from standard components of certain types
- Easy and fast to use being both conceptually and practically simple and requiring a minimum of labour
- Reversible whereby it is possible to replace standard components of existing modular plasmids after their construction, without the need to re-build the entire plasmid from scratch
- Extensible in that addition of one or more components outside the standard types is straightforward
Replicons, selectable markers, and application-specific modules have been incorporated into the kit. The pMTL80000 series is a standard arrangement in which every plasmid contains exactly one module of each of four types, always arranged in the same order, and always bounded by the same four rare (8 bp) type II restriction enzyme recognition sites. This system allows for the quick and easy modification of existing pMTL80000-based plasmids.
The modular system was developed by the Minton group at the University of Nottingham, and is published (Heap et al, 2009). The system has been extensively tested at the University of Nottingham and continues to be expanded. An updated publication for the Minton lab outlines up-coming technologies available for the modular plasmids (Minton et al, 2016).
- Heap, J.T. et al. A modular system for Clostridium shuttle plasmids. J Microbiol Methods. 78, 79-85 (2009).
- Minton, N.P. et al. A roadmap for gene system development in Clostridium. Anaerobe. 41, 104-112 (2016).