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The very end of mRNA is polyadenylated as usual, but the BNT162b2 vaccine ends the following sequence, as denoted in this article:

                                     ****** ****
UAGCAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAGCAUAU GACUAAAAAA AAAAAAAAAA 
AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAA

This is 30 A’s, then a “10 nucleotide linker” (GCAUAUGACU), followed by another 70 A’s.

What is the reason for this design choice?

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To enhance stability and translation efficiency according to {1}:

The 5′UTR (TEV) [8,21] and 3′ UTR (F-I) of this construct have been shown to enhance stability and translation efficiency, as has the 100-nucleotide poly(A) tail interrupted by a short linker (A30LA70, where L = GCAUAUGACU) [22]


References:

  • {1} Stadler, C., Bähr-Mahmud, H., Celik, L. et al. Elimination of large tumors in mice by mRNA-encoded bispecific antibodies. Nat Med 23, 815–817 (2017). https://doi.org/10.1038/nm.4356 https://www.nature.com/articles/nm.4356
  • {21} Gallie, D.R., Tanguay, R.L. & Leathers, V. Gene 165, 233–238 (1995).
  • {22} Vallazza B, Petri S, Poleganov MA, Eberle F, Kuhn AN, Sahin U. Recombinant messenger RNA technology and its application in cancer immunotherapy, transcript replacement therapies, pluripotent stem cell induction, and beyond. Wiley Interdiscip Rev RNA. 2015 Sep-Oct;6(5):471-99. doi: 10.1002/wrna.1288. Epub 2015 Jun 9. PMID: 26061157. https://pubmed.ncbi.nlm.nih.gov/26061157/
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    $\begingroup$ It’s curious that, as far as I can see, reference 22 doesn’t mention linkers in the poly(A) tail at all. $\endgroup$ – canadianer Dec 27 '20 at 1:58
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    $\begingroup$ @canadianer yes I got stuck there too… next steps is likely to email Stadler, C., Bähr-Mahmud, H., Celik, L. et al. They might have mixed up some references. $\endgroup$ – Franck Dernoncourt Dec 27 '20 at 2:00
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    $\begingroup$ Patent referring to that linker: patents.google.com/patent/JP2018525410A/en $\endgroup$ – Klaws Dec 31 '20 at 18:46

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