Future mRNA therapies could be redesigned to prevent potentially harmful immune responses, according to a British study confirming the safety of mRNA vaccines used during the COVID-19 pandemic.
Its authors found that misreading therapeutic mRNA (messenger RNA) from the cell's decoding mechanism can trigger an adverse immune response in the body.
Researchers have identified the sequence in this type of RNA that is responsible and found a way to prevent "non-target" immune reactions to allow safer design of future mRNA therapies.
Scientists behind COVID-19 vaccine are this year's Nobel Prize winners in medicine or physiology
Ribonucleic acid (mRNA) is the genetic material that tells cells in the body how to produce a particular protein. Researchers from the Medical Research Council's (MRC) Department of Toxicology have found that the cellular mechanism that "reads" mRNA "slips" when confronted with repeats of chemical modification common in mRNA therapies.
In addition to the target protein, these gaps lead to the production of "non-target" proteins that trigger an unintentional immune response.
MRNA vaccines are believed to have "changed the game." They have been used to contain the COVID-19 pandemic and have already been proposed for the treatment of various cancers, cardiovascular, respiratory and immunological diseases in the future.
This revolutionary class of therapeutics was made possible in part by the work of biochemist Catalin Carrico and immunologist Drew Weissmann. They demonstrated that by adding chemical modifications to the bases - the building blocks of mRNA, synthetic versions of it can bypass some of our body's immune defenses, allowing the therapeutic agent to enter the cell and take its toll. This discovery earned them this year's Nobel Prize in Physiology or Medicine.
The latest developments under the direction of biochemist Professor Ann Willis and immunologist Dr James Taventiran of the University of Cambridge build on previous advances to ensure the prevention of any safety issues associated with future mRNA-based therapies.
In a study published in p. "Nature", the authors describe the mechanism responsible for the "slips" in question.
In collaboration with researchers from the Universities of Kent, Oxford and Liverpool, scientists have looked for evidence of the production of "non-target" proteins in people who received Pfizer's mRNA vaccine against COVID-19.
Researchers found that a third of the 21 patients who were vaccinated had an unintended immune response, but no ill effects. This is consistent with the extensive safety data available for these COVID-19 vaccines.
The team then redesigned the mRNA sequences to avoid these "off-target" effects, correcting error-prone genetic sequences in synthetic mRNA. In this way, the desired protein is obtained. Similar design modifications can easily be applied to future mRNA vaccines to achieve the desired effects while preventing dangerous and unforeseen immune reactions.
"Research has undeniably shown that mRNA vaccination against COVID-19 is safe. "Billions of doses of Modern's and Pfizer's mRNA vaccines have been safely delivered, saving lives around the world," the team said.
"We need to ensure that future mRNA vaccines are just as reliable. Our demonstration of "slip-resistant" mRNA is a vital contribution to the future safety of this drug platform. These new therapies are promising for the treatment of a wide range of diseases."
The use of synthetic mRNA for therapeutic purposes is tempting, as its production is cheap and can solve the problem of significant inequality in health care around the world by making these drugs more affordable. In addition, synthetic mRNAs can be changed quickly - for example, to create a new variant of a COVID-19 vaccine.
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