A promising approach to treating disease involves delivering therapeutic mRNA into the patient’s cells, and letting the cells take it from there, translating the mRNA into a protein. The mRNA delivered in this way is specifically designed to code for a protein that corrects for the deficient version that causes the patient’s disease. Importantly, mRNA treatment is more efficient than typical DNA treatments such as gene therapy because mRNA, unlike DNA, does not need to enter the nucleus. Also, mRNA expression is transient and does not pose the risk of permanently altering the patient’s genome through insertional mutagenesis, as can happen with some DNA therapies (1).
A challenge to mRNA therapy, however, involves the instability of RNA, which is easily degraded. Recent progress on this front has been made by a group of researchers led by Dr. Paula T. Hammond in the Department of Chemical Engineering at MIT. The group has developed an enhanced, more efficient mRNA delivery system for the purpose of vaccinations and disease treatment. The current delivery system involves carriers that facilitate the uptake of the mRNA molecules, but also decrease the mRNA’s ability to bind a protein called PABP, or poly-A binding protein. PABP stabilizes mRNA and initiates its translation by stimulating its binding to the cellular ribosomes. The inability to bind PABP decreases mRNA translation and increases mRNA degradation, thereby lowering the effectiveness of the therapy. The MIT research team has engineered a recombinant form of PABP at a 10:1 PABP/mRNA ratio and delivers the complex within neutralizing polyamines that possess side chains that stabilize the PABP complex, increase the internalization of mRNA, and degrade after delivery. In other words, the research team has improved the efficacy of the delivery of mRNA treatments by developing a technique based on the cell’s natural mechanisms of translation. This research on synthetic co-delivery of mRNA can also be applied to siRNA, miRNA, aptamers, and DNA plasmids, thereby increasing not only the efficacy of treatments, but also the number of diseases that can be treated in this way. The discovery holds much potential for exciting new disease therapies (1).
- Li, J., He, Y., Wang, W., Wu, C., Hong, C., Hammond, P. (2017, September 19). Assembly of Ribonucleoproteins for Enhanced mRNA Delivery. Retrieved from http://onlinelibrary.wiley.com/doi/10.1002/anie.201707466/full.