Nonsense variants and the therapies aimed at them

A protein that stops too soon.

A nonsense variant stops a protein early. RiboRescue compares three rescue routes—and shows where the evidence runs out.

71,378pathogenic nonsense variants examined
3possible rescue routes compared
3 of 3conditions the positive control met
01

The problem

A gene is a sentence. This is a full stop in the middle.

Genes are read in three-letter codons. A nonsense variant turns an amino-acid codon into an early stop.

protein builtpremature stopnever built

The cell may also destroy the message. A therapy therefore needs both surviving RNA and readthrough.

02

The three routes

Three ways out, and they are not equally knowable.

One route is uncertain, one unvalidated, and one geometrically decidable.

Route one

Small-molecule readthrough

Six drugs are predicted, but their uncertainty intervals overlap almost everywhere. They cannot be ranked honestly.

Predicted, but not separable

Route two

Suppressor tRNA

A custom adapter restores one amino acid at one stop. Public data do not yet validate it.

Designable, but unvalidated

Route three

Base editing

DNA-letter geometry is decidable from sequence: 22,042 of 70,660 scoreable variants are reachable.

Decidable from sequence

03

Where to go

Six questions, six places to look.

Each page answers one question, keeps its denominator, and avoids a composite treatment score.