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What is the role of readthrough therapy for nonsense mutations?

Suppressing translation termination selectively at PTCs (also referred to as readthrough) is a potential treatment strategy for genetic diseases caused by nonsense mutations, including CF13. Readthrough agents suppress termination at in-frame PTCs by promoting the accommodation of near-cognate aminoacyl-tRNAs into the ribosomal acceptor (A) site.

What is the ribosome readthrough score?

The Ribosome ReadThrough Score (RRTS) was defined as the density of ribosomes in the 3´-UTR between the NTC and the first in-frame 3′-termination codon divided this value by the density of ribosomes in the CDS for every annotated transcript (as previously described36).

Does sri-41315 improve readthrough efficacy in human airway cells?

These findings clearly indicate that improvements in readthrough efficacy and pharmacologic properties of SRI-41315 were sufficient to enable translation to human airway cells that natively express CFTRtranscripts with PTCs that are subject to NMD.

Do aminoglycosides induce readthrough in cystic fibrosis?

Proof-of-principle studies show that aminoglycosides can induce readthrough in a variety of disease contexts, including CF, where a subset of aminoglycosides restore partial CFTR activity in vitro and in vivo18–24.


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