Scientists at Hong Kong University of Science and Technology came up with a technique to increase the efficiency and potentially the efficacy of mRNA therapeutics. mRNA molecules have what is called a poly-A tail, which is basically a string of adenine nucleotides at one end. These researchers discovered that by replacing some of these nucleotides in the mRNA tail with cytidine, a cytosine base with a ribose sugar attached, that they could enhance the resulting protein production of the mRNA and increase its stability and life-span. The technique could lead to more effective mRNA therapies and vaccines, potentially enabling clinicians to achieve similar or better effects with smaller doses.
mRNA therapies have come a long way in just the last few years. The COVID-19 pandemic has propelled this approach from an emerging technology to a mainstay of our vaccine response. The concept is elegant – deliver mRNA strands to the patient, and allow their own cellular machinery to produce the relevant protein that the strands code for. So far, so good – the approach, once considered unrealistic because of the fragility of mRNA, has proven to work very well, at least for COVID-19 vaccines.
However, there is always room for improvement. One of the issues with current mRNA therapies is that they can require multiple rounds of dosing to create enough of the therapeutic protein to achieve the desired effect. Think of the multiple injections required for the COVID-19 vaccines. Creating mRNA therapies that can induce our cells to produce more protein would certainly be beneficial.
To address this limitation, these researchers have found a way to modify the poly-A tail of synthetic mRNA strands. They found that by replacing some of the adenosine in the mRNA tail with cytidine, they could drastically increase the amount of protein the resulting strands ended up producing when applied to human cells and in mice. This translated to 3-10 times as much protein when compared with unmodified mRNA.
The researchers hope that the approach can enhance the effectiveness and required dosing schedules for mRNA therapies.
“Increasing the protein production of synthetic mRNA is generally beneficial to all mRNA drugs and vaccines,” said Becki Kuang, a researcher involved in the study. “In collaboration with Sun Yat-Sen University, our team is now exploring the use of optimized tails for mRNA cancer vaccines on animal. We are also looking forward to collaborating with pharmaceutical companies to transfer this invention onto mRNA therapeutics and vaccines’ development pipelines to benefit society.”
See a short animation about the technology below.
Study in journal Molecular Therapy – Nucleic Acids: Cytidine-containing tails robustly enhance and prolong protein production of synthetic mRNA in cell and in vivo