Retron Arrays Enable Multi-Site Genome Editing

American researchers have developed the multitron system, leveraging bacterial retrons to produce multiple editing donors from a single transcript. This technology allows for precise, concurrent modifications at multiple genomic sites in both prokaryotic and eukaryotic cells. The approach was validated through molecular recording, genetic element minimisation, and metabolic engineering applications.

The multitron system uses arrays of retron-derived donor DNA to edit multiple genome sites simultaneously. This contrasts with traditional methods that typically involve laborious cycles of single-site edits. The study demonstrated the method’s efficacy in bacteria, editing up to five target sites with varying efficiencies.

Additionally, the system was adapted for use in eukaryotic cells, combining retron arrays with CRISPR-Cas9 technology for precise genome modifications. The researchers successfully applied this technology to metabolic engineering, notably increasing lycopene production in bacterial cultures.

In human cells, the multitron system showed significant potential by enabling precise editing of multiple non-adjacent genomic sites concurrently. This advancement addresses the complex challenge of introducing combinatorial mutations within a single genome, facilitating studies on gene interactions and functional genomics.

The ability to perform multiplexed edits in human cells without the need for iterative editing cycles enhances the efficiency and scope of genetic research and therapeutic developments.

The study was led by Seth Shipman from the Gladstone Institute of Data Science and Biotechnology at the University of California, San Francisco. It was published today in Nature Chemical Biology.