# Enhancement of prime editing by recruiting engineered or evolved components and implementing novel strategies

## TL;DR

This review discusses ways to improve prime editing, a CRISPR-based gene editing method, to make it more efficient for treating genetic disorders.

## Contribution

The paper reviews recent advancements in prime editing components and strategies to enhance editing efficiency and therapeutic potential.

## Key findings

- Modifications to Cas9, reverse transcriptase, or PegRNA can boost prime editing efficiency.
- Directed evolution and rational design improve the performance of prime editors.
- Epigenetic modifiers can further enhance editing efficiency for gene therapy applications.

## Abstract

Prime editing has recently gained attention for its promising potential in treating genetic disorders caused by different types of mutations. This method, based on Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), has led to the development of new strategies that offer improved editing efficiency. Additionally, the components of prime editing—namely, the prime editor (PE) and the prime editing guide RNA (PegRNA)—have been enhanced through rational design and direct evolution of structural modifications. These improvements have resulted in better performance and new capabilities, driven by novel mutations or components. In this review, we compare various studies that report enhanced versions of PE or PegRNA, which achieve more efficient results. These advancements hold the potential to accelerate and simplify the development of gene therapies for a range of genetic disorders.

•Optimizing Prime Editing: Boosting efficiency by modifying Cas9, RT, or PegRNA.•Advancing via Design: Directed evolution & rational design improve editing potential.•Epigenetic Modifiers Help: Enhance efficiency, expanding gene therapy applications.•Delivery Challenges: Efficient targeting remains key for clinical use.

Optimizing Prime Editing: Boosting efficiency by modifying Cas9, RT, or PegRNA.

Advancing via Design: Directed evolution & rational design improve editing potential.

Epigenetic Modifiers Help: Enhance efficiency, expanding gene therapy applications.

Delivery Challenges: Efficient targeting remains key for clinical use.