Figure 6.

Amplifiers stabilize the CFTR mRNA and thereby increase translation, enlarging the pool of immature CFTR protein. Amplifiers (red) are of particular interest for the treatment of Class II and V mutations. Top: Class II mutations are misfolded and only a fraction reaches the plasma membrane, even in the presence of CFTR correctors (blue). Amplifiers provide more immature protein that can subsequently be rescued with CFTR modulators. Bottom: Class V mutations introduce cryptic splice sites, resulting in a mix of normal and alternatively spliced (yellow) CFTR mRNA. The fraction of normal mRNA gives rise to wild-type CFTR, but the number of channels is severely reduced. Enhancing the number of correct mRNA transcripts results in more CFTR protein at the PM.