# Evolution of Prime Editing: Enhancing Efficiency and Expanding Capacity

**Authors:** Jihyeon Yu, Ju‐Chan Park, Heesoo Uhm, Yong‐Woo Kim, Hyeon Woo Im, Sangsu Bae

PMC · DOI: 10.1002/advs.202521015 · Advanced Science · 2026-02-11

## TL;DR

Prime editing is a promising genome editing tool that allows precise mutations without DNA breaks, but it needs improvements in efficiency and capacity for broader use.

## Contribution

This review summarizes recent efforts to enhance prime editing's efficiency and expand its capabilities for clinical applications.

## Key findings

- Prime editing can induce insertions, deletions, and point mutations without DNA double-strand breaks.
- Current limitations include low editing efficiency and limited scalability for large-scale genetic manipulation.
- Ongoing research focuses on improving prime editing tools for better therapeutic potential.

## Abstract

Genetic mutations cause approximately 80% of rare human diseases, highlighting the urgent need for precise genome editing. Since clustered regularly interspaced short palindromic repeat (CRISPR)‐CRISPR‐associated 9 (Cas9) nucleases were first used for genome editing in 2012, genome editing technologies have rapidly advanced. Base editors, derived from the CRISPR‐Cas system, were developed to introduce specific point mutations without requiring DNA double‐strand breaks, and subsequently, prime editing (PE) technology was created to enable insertions, deletions, and all types of point mutations. The precision and versatility of PE make it a promising tool for clinical applications. However, PE has potential limitations, including low editing efficiency and limited capacity for large‐scale manipulation. To overcome these limitations, research has been continuously conducted to improve PE efficiency and expand its capabilities. Therefore, this review aims to highlight current efforts and future directions for developing and improving PE‐related tools.

Most rare diseases are caused by genetic mutations. Prime editing (PE) has emerged as a versatile tool capable of inducing diverse mutations without generating DNA double‐strand breaks. Despite its significant clinical potential, PE faces limitations in terms of efficiency and scalability. This review examines recent advances and future research directions aimed at improving and expanding PE‐related tools for therapeutic applications.

## Linked entities

- **Proteins:** cas9 (type II CRISPR RNA-guided endonuclease Cas9)

## Full-text entities

- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13042712/full.md

## References

98 references — full list in the complete paper: https://tomesphere.com/paper/PMC13042712/full.md

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Source: https://tomesphere.com/paper/PMC13042712