Technical Note: Improved total protein expression and duration with ModTail™ technology, a novel poly(A) tail modification

mRNA modifications, such as the 5′ cap and the use of modified nucleotides were key to the success of mRNA vaccines. However, it is widely recognized that further innovations are required to optimize mRNA molecules to meet the requirements for wider therapeutic applications.

This technical note introduces the ModTail™ technology, TriLink's novel poly(A) tail modification, which is shown to increase total protein expression and extend the duration of expression of various N1-methylpseudouridine (N1MePsU)-mRNA constructs in both in vitro cell assays and in vivo studies using mice.

We present the following in this tech note:

ModTail chemistry is added to mRNA with high efficiency and with no measurable impact on mRNA capping efficiency, purity, or dsRNA levels

Compatibility of ModTail chemistry with various cap structures, tail lengths, and types of mRNA constructs

ModTail mRNA increases in vitro and in vivo protein expression and duration of expression

The possibility that higher protein expression with ModTail possibly lowers the dosage of mRNA needed to provide the same therapeutic effect

TECHNICAL NOTE

Improved total protein expression and duration with ModTail™ technology, a novel poly(A) tail modification