Researchers Enhance Safety of mRNA Therapeutics by Preventing Unintended Immune Responses

Modified mRNA sequences prevent 'off-target' effects, paving the way for safer future mRNA vaccines.

Researchers have discovered that misreading of therapeutic mRNAs by the cell's decoding machinery can cause an unintended immune response in the body.
The researchers identified that bases with a chemical modification called N1-methylpseudouridine, which are currently contained in mRNA therapies, are responsible for the 'slips' along the mRNA sequence.
An unintended immune response occurred in one-third of the 21 patients in the study who were vaccinated with the mRNA Pfizer vaccine against COVID-19, but with no ill-effects.
The team then redesigned mRNA sequences to avoid these 'off-target' effects, by correcting the error-prone genetic sequences in the synthetic mRNA.
Such design modifications can easily be applied to future mRNA vaccines to produce their desired effects while preventing hazardous and unintended immune responses.