# Recruitment and rejoining of remote double-strand DNA breaks for enhanced and precise chromosome editing

## TL;DR

This paper introduces a CRISPR-based method called HRMR that improves the precision and efficiency of editing chromosomes, which could help in studying and treating genetic diseases.

## Contribution

The novel HRMR strategy uses homologous donor templates to significantly enhance the efficiency and accuracy of chromosomal rearrangements.

## Key findings

- HRMR achieves over 95% homologous recombination efficiency.
- The method works across multiple loci and cell lines.
- Live-cell imaging shows homologous donors increase chromosome end proximity.

## Abstract

Chromosomal rearrangements, such as translocations, deletions, and inversions, underlie numerous genetic diseases and cancers, yet precise engineering of these rearrangements remains challenging. Here, we present a CRISPR-based homologous recombination-mediated rearrangement (HRMR) strategy that leverages homologous donor templates to align and repair broken chromosome ends. HRMR improves efficiency by approximately 80-fold compared to non-homologous end joining, achieving over 95% homologous recombination. Validated across multiple loci and cell lines, HRMR enables efficient and accurate chromosomal rearrangements. Live-cell imaging reveals that homologous donors mediate chromosome end proximity, enhancing rearrangement efficiency. Thus, HRMR provides a powerful tool for disease modeling, chromosomal biology, and therapeutic applications.

The online version contains supplementary material available at 10.1186/s13059-025-03523-8.