What is DEVISE?
DEVISE (Drug Delivery System via Type VI Secretion System) is a novel drug delivery method developed by SUSTech Shenzhen 2023. By co-opting a bacterial type VI secretion system, DEVISE can achieve stable, standing and self-regulated polypeptide drug release.
Peptide drugs have increased in popularity in an expanding market that targets diseases related to endocrinology, metabolism, and oncology.
Peptide drugs have become a mainstay of drug design due to their high specificity, good efficacy, low immunogenicity, and low toxicity.
Can you imagine that one day, people can drink a bottle of juice containing bacteria (just like yogurt) to cure their diseases and researchers can easily deliver their peptides into cells?
However, in practice, the poor stability in vivo and weak membrane permeability limit the function of some peptide drugs, especially for those who require direct delivery into the cytosol.
Bearing that in mind, we try to find a way to solve the problem. Here it is – the type six secretion systems (T6SS) of gram-negative bacteria.
The type six secretion system (T6SS) is one of the secretion systems that can deliver effectors through T6SS proteins. Previous research has mentioned that T6SS can also carry effectors from other bacteria or even Cre proteins.
The bacteria we try to use in our project are Vibrio cholerae and Pseudomonas aeruginosa. Sounds horrible? Don’t worry, we have tried our best to decrease the toxicity in our project so that it will be safe to use.
By using the injection characteristics of the type six secretion systems (T6SS), the virulence factors of bacteria were modified to construct the drug secretion model. Imagine a type six secretory system (T6SS) is like a syringe. Once it is folded inside the bacteria, it can reach out, puncture the surrounding cells, and inject the protein into their cytoplasm, which is exactly what we want it to do. Secretory systems and bacteria are the perfect combination of syringe and capsule.
Bacteria can live in a specific location in the body, store polypeptide drugs, and achieve long-term stable targeted drug delivery through the type 6 secretion system (T6SS). We hope to use this sophisticated organism to achieve stable, standing, and self-regulating drug release control. This would be a boon for people with chronic conditions who need to take medication for a long time.
Our project may provide a new way to test and deliver peptides. This new drug delivery system offers a hope for the development of drug treatments. Perhaps our efforts can pave a brick for it. If you’re interested, click the button to learn more.
References
1. Muttenthaler, M.; King, G.F.; Adams, D.J.; Alewood, P.F. Trends in peptide drug discovery. Nat Rev Drug Discov 2021, 20, 309-325, doi:10.1038/s41573-020-00135-8.
2. Wang, L.; Wang, N.; Zhang, W.; Cheng, X.; Yan, Z.; Shao, G.; Wang, X.; Wang, R.; Fu, C. Therapeutic peptides: current applications and future directions. Signal Transduct Target Ther 2022, 7, 48, doi:10.1038/s41392-022-00904-4.
3. Costa, T.R.D.; Felisberto-Rodrigues, C.; Meir, A.; Prevost, M.S.; Redzej, A.; Trokter, M.; Waksman, G. Secretion systems in Gram-negative bacteria: structural and mechanistic insights. Nat Rev Microbiol 2015, 13, 343-359, doi:10.1038/nrmicro3456.
4. Hersch, S.J.; Lam, L.; Dong, T.G. Engineered Type Six Secretion Systems Deliver Active Exogenous Effectors and Cre Recombinase. mBio 2021, 12, e0111521, doi:10.1128/mBio.01115-21.
5. Ho, B.T.; Fu, Y.; Dong, T.G.; Mekalanos, J.J. Vibrio cholerae type 6 secretion system effector trafficking in target bacterial cells. Proc Natl Acad Sci U S A 2017, 114, 9427-9432, doi:10.1073/pnas.1711219114.
6. Wu, L.-L.; Yan, S.; Pei, T.-T.; Tang, M.-X.; Li, H.; Liang, X.; Sun, S.; Dong, T. A Dueling-Competent Signal-Sensing Module Guides Precise Delivery of Cargo Proteins into Target Cells by Engineered Pseudomonas aeruginosa. ACS Synth Biol 2023, 12, 360-368, doi:10.1021/acssynbio.2c00441.
7. Retrieved from https://www.insightaceanalytic.com/report/global-peptide-cdmo-pharmaceutical-market-/1202