简单说明
Your DNA is the master copy; RNA is the working printout the cell actually reads. RNA editing corrects the printout instead of the master. The correction is genuine while it lasts, but the cell keeps printing fresh copies from the unchanged original, so the treatment has to be repeated. In exchange you get something genome editing cannot offer: if it goes wrong, it stops.
深入了解
Programmable RNA editing recruits adenosine deaminases acting on RNA (ADAR) — either introduced as a dCas13-ADAR fusion, as in REPAIR and RESCUE, or endogenous ADAR recruited by an engineered guide RNA alone — to convert adenosine to inosine at a chosen position. Inosine is read as guanosine, giving an effective A→G change in the transcript. Guide-only approaches avoid delivering any protein at all, which is a meaningful advantage for redosing.
The trade-off, stated plainly
Permanence is the whole argument. A DNA edit is one treatment and a lifetime of consequence, good or bad. An RNA edit is a repeated treatment and a reversible consequence. Which is preferable depends entirely on the disease, the patient and how confident anyone can reasonably be about a permanent change.
Where it stands
Several companies are pursuing ADAR recruitment clinically, with alpha-1 antitrypsin deficiency a common first indication because the target is in the liver and the biomarker is measurable. No RNA-editing medicine has been approved.
Sources
- Science (Cox et al.) · 2017
RNA editing with CRISPR-Cas13 ↗