Researchers have developed a groundbreaking approach called LEGO that allows for the systematic optimization of mRNA molecules, paving the way for highly effective and targeted treatments for a variety of medical conditions.
Maximizing mRNA’s Potential
The public use of messenger RNA (mRNA) to provide emergency protection from COVID-19 using mRNA in vaccines instantly validated the powerful promise of mRNA therapeutics. Now researchers at the Broad Institute of MIT and Harvard, along with colleagues at the Massachusetts Institute of Technology (MIT), have pushed this opportunity to the next level by building a new framework dubbed LEGO.
LEGO is the acronym for ‘ ligation-enabled messenger RNA-oligonucleotide assembly’, an approach that allows scientists to chemically modify mRNAs by a manipulating their chemical structure sequence, to influence their interaction with the cell´s protein-translation machinery. This, in turn, allows them to achieve the therapeutic effects they want: increased production of the protein or longer-term expression of this particular protein.
Unlocking the Secrets of mRNA Medicine
The LEGO framework has the power to change the world of mRNA medicine. Using this protocol, the researchers can now systematically test hundreds of different chemical modifications to mRNA and directly measure how each one affects protein translation for each component of an mRNA drug.
By adopting LEGO, scientists can adjust specific mRNAs´ half-lives and translational values to target how a particular therapeutic will work. In other words, using engineered approaches they can make mRNA-based therapies that generate more protein or keep the protein on for longer at lower doses with less toxicity.
The resulting projects are already demonstrating strong effect sizes — an mRNA hormone replacement therapy that causes 8x higher protein expression compared to regular, and an optimized COVID-19 vaccine causing a 17-fold greater antibody response compared to typical.
Conclusion
The LEGO platform created by Broad Institute and MIT researchers is revolutionary because it could enable mRNA-based therapies to realize their full potential. Through the meticulous manipulation of mRNA, they are laying down a blueprint for an entirely new age in highly potent and precise medications across an array of diseases from cancer and hemophilia to diabetes and beyond. “Today is a great day for science and humanity,” said Albert Bourla, Chairman and CEO, Pfizer. “We are reaching this critical.
