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European Biopharmaceutical Review

The Secret Sauce

Development of the new class of vaccines based on mRNA has been a game changer. Robert Langer, of MIT, calls it a tremendous vindication for everyone working on controlled drug delivery. Speedy development and distribution of the mRNAbased COVID-19 vaccines belies the decades of experimentation needed to field a reliable and safe delivery system for this new class of medications.

The basic principle of mRNA vaccines is relatively straightforward though easier said than done. mRNA encoding is introduced into the cytosol of target cells, where it is translated by ribosomes into antigenic proteins. These antigens stimulate production of neutralising antibodies. From the outset, delivery proved to be a significant hurdle. mRNA molecules are thousands of times larger than the small molecule drugs that are easily able to enter cells by diffusion. Moreover, it is short-lived in vivo inactivated by ubiquitous nucleases in blood and cytosol.

Delivering intact large nucleotides, such as mRNA, into a living cell is like the perfect crime: disguise yourself, get in undetected, and do the deed. Beyond sheer size, the negative-charged backbone of mRNA and other nucleotides is repelled by the anionic character of the cell membrane, therefore, preventing close approach and uptake. Clearly, what is needed is a delivery vehicle that shields the mRNA, allowing for its uptake by the cell, prevents its degradation along the way, and allows its release in the cytosol, where it can be translated, as intended.

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Emile Bellott is a member of the EBR Industry Advisory Board, a graduate of the Harvard Business School, US, and an industry consultant with experience in the biotech and biopharma industry.

atlanticinstitute@gmail.com
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Emile Bellott
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