Nature nanotechnologyJun 15, 2026

Efficient gene editing inside living organisms and in lab tests using fat-based particles

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 16, 2026

Abstract

A single dose of 2 mg/kg of the optimized prime editing lipid nanoparticles achieved 49% average in vivo prime editing in the bulk mouse liver.

The developed prime editing lipid nanoparticles (PE-LNPs) effectively addressed key challenges that limited editing efficiency.
Application of PE-LNPs in a mouse model corrected the PAH R408W mutation, a known cause of phenylketonuria.
Prime editing efficiencies and serum phenylalanine levels reached are anticipated to be curative.
PE-LNPs showed reduced off-target editing compared to conventional DNA delivery methods.
Transient elevation of liver enzymes was observed, with no long-term toxicity recorded.
PE-LNPs can be administered repeatedly to further enhance editing efficiencies.

Simplified

Prime editing is a versatile clinical genome editing method that enables precise substitutions, small insertions and deletions at specified locations in the genomes of living systems including human cells. Although non-viral lipid nanoparticle (LNP) delivery of RNA in vivo has become a preferred method for gene editing in animals and patients, its application to complex, three-component prime editing systems has yielded low editing efficiencies. Here we developed a systematic prime editing LNP (PE-LNP) optimization platform that addresses key bottlenecks in cargo design that limit editing efficiency. This generalizable workflow yielded PE-LNPs that can achieve 49% average in vivo prime editing in the bulk mouse liver with a single dose of 2 mg kg. We applied our workflow to the correction of PAH R408W, a cause of phenylketonuria, in a mouse model and achieved prime editing efficiencies and serum phenylalanine levels anticipated to be curative. We also show that PE-LNPs minimize off-target editing compared with DNA delivery methods, induce only transient elevation of liver enzymes and can be dosed repeatedly to improve editing efficiencies. These PE-LNP systems provide an attractive alternative to viral delivery by offering transient expression that minimizes off-target editing, no observed long-term toxicity and high levels of non-viral in vivo liver prime editing. -1