Novel approach increases the protein production efficiency of synthetic mRNAs

A group of synthetic biologists at the Hong Kong University of Science and Technology (HKUST) recently figured out a way to improve the efficiency of synthetic mRNA protein production by up to tenfold. This means that the efficiency of mRNA vaccines and drugs—such as those used against cancer, Covid-19, or other genetic diseases—will be significantly increased with even less mRNA dosage.

Novel approach increases the protein production efficiency of synthetic mRNAs
The research team led by Prof. Becki KUANG (middle) and PhD candidates Jacky LI (right) and Orion LIANG hopes to collaborate with pharmaceutical companies to apply their mRNA tail sequence optimization technology on mRNA drugs and vaccines. Image Credit: HKUST

As mRNAs can be produced to instruct human cells to produce any type of protein, such as antigens, enzymes, and hormones, which are vital in combating infections and regulating biological functions, mRNA is undoubtedly a preferred alternative for vaccines and disease treatment.

However, high doses and repeated injections are frequently required for mRNA drugs and vaccines in order to produce adequate quantities of protein in the body, so improving mRNA’s effectiveness—such as by increasing its protein production efficiency—is a hot topic among scientists, as the immune system, for instance, could work better with more specific antibodies.

Now, a team led by Prof. Becki Kuang Yi, Assistant Professor in the Department of Chemical and Biological Engineering at HKUST, has developed a means to extend the life and efficacy of mRNA.

Prof. Kuang’s team produced several mRNA tail sequences and ultimately found optimized sequences that could produce three to ten times as many proteins as unoptimized tail sequences routinely utilized for synthetic mRNAs on both human cells and mice. It also doubles the time it takes to produce proteins.

This innovative method will not only minimize the amount and number of injections required for mRNA drugs and vaccinations but it may also lower treatment costs. It can also be used in conjunction with other mRNA enhancement technologies to increase protein output in a synergistic manner.

Increasing the protein production of synthetic mRNA is generally beneficial to all mRNA drugs and vaccines. 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.”

Becki Kuang Yi, Assistant Professor, Department of Chemical and Biological Engineering, Hong Kong University of Science and Technology

The study was published in the journal Molecular Therapy - Nucleic Acids.

mRNA drugs and vaccines have received a lot of attention in recent years because of their success in protecting humans from severe cases of infectious diseases like COVID-19 and their tremendous promise in treating chronic diseases like cancer. According to previous research, the worldwide mRNA therapeutics market was valued at USD 39.90 billion last year and is predicted to grow further in the future decade.

Source:
Journal reference:

Li, C. Y., et al. (2022) Cytidine-containing tails robustly enhance and prolong protein production of synthetic mRNA in cell and in vivo. Molecular Therapy - Nucleic Acids. doi.org/10.1016/j.omtn.2022.10.003.

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