Molecular therapy. Nucleic acidsJul 24, 2025

Precise gene editing inside living mice to fix disease models

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 2, 2026

Abstract

Base editing has been evaluated in 66 mouse disease models for its efficiency and therapeutic potential.

Base editing allows for precise conversions of nucleotides without causing double-stranded breaks.
Editing efficiencies are affected by factors such as enzyme design, delivery method, and sequence context.
Significant functional improvements have been observed, including extended survival in severe genetic conditions.
Base editing is limited to correcting single-nucleotide variants and has a restricted editing window relative to the PAM site.
Emerging delivery methods, such as lipid nanoparticles, may enhance the effectiveness of base editing.

Simplified

CRISPR base editing enables precise, irreversible base conversions without inducing double-stranded breaks (DSBs) and has gained significant attention in recent years. By converting cytosine to thymine (C→T) or adenine to guanine (A→G), base editors (BEs) efficiently correct pathogenic single-nucleotide variants (SNVs). This review examinesmouse disease models-assessing editing efficiency, phenotypic rescue, and therapeutic potential across 66 studies. A key challenge in base editing is optimizing delivery. Most studies rely on split-intein dual adeno-associated virus (AAV) vectors due to BEs exceeding AAV packaging limits, though lipid nanoparticle (LNP) delivery is emerging. Editing efficiencies vary widely, influenced by enzyme design, delivery method, and sequence context. Many studies show significant functional gains, including extended survival in severe models such as FAH-deficient tyrosinemia type I and Hutchinson-Gilford progeria, restored dystrophin in Duchenne muscular dystrophy, and cognitive improvement in neurodegenerative models. Despite advantages such as reduced indels and increased precision, base editing is restricted to SNV correction and targets only a limited editing window relative to a protospacer adjacent motif (PAM) site. Advances in enzyme engineering, delivery strategies, and hybrid approaches incorporating prime editing could broaden its applications. As base editing evolves, its success in preclinical models positions it as a key player in next-generation gene therapies. in vivo

Full Text

We can’t show the full text here under this license.

View Full Text ↗

Precise gene editing inside living mice to fix disease models

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the crispr gene editing brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the crispr gene editing brief