Researchers are making waves in the field of genetic editing with the introduction of the extended prime editor system, known as EXPERT, which significantly enhances both the efficiency and the editing range for large fragment modifications. Traditional prime editing systems (PE) have already demonstrated potential for high-precision edits, but they have been limited by their inability to edit upstream from the target site efficiently.
The EXPERT system effectively overcomes this limitation by incorporating an extended version of the prime editing guide RNA (pegRNA) and the addition of another sgRNA, which creates strategic nicks on the DNA strand. This innovation allows EXPERT to modify sequences not just downstream but also upstream of the pegRNA nick, substantially raising the bar for what prime editing can achieve.
Through their tests, researchers discovered EXPERT’s unmatched capacity to amend sequences up to 88 base pairs and insert sequences up to 100 base pairs within the upstream area of the pegRNA nick. Compared to existing prime editors like PE2, EXPERT exhibited improvements by as much as 3.12-fold, achieving editing efficiencies up to 122.1 times higher for large fragment edits.
One of the most significant advantages of the EXPERT system is its safety profile. Research confirms the utilization of the ups-sgRNA does not result in increased rates of undesired insertions and deletions (indels). The dual nicks generated by EXPERT are located on the same DNA strand (cis nicks), which minimizes the chances of off-target effects—a common concern with traditional PE systems.
The experiments conducted showed consistent low indel rates at the targeted sites, ensuring the precision of edits remains high. This control over unintended alterations raises the confidence for researchers and practitioners alike, making EXPERT not just more capable but also safer.
“EXPERT can efficiently perform editing on both sides of the ext-pegRNA nick, which is unattainable by canonical PEs,” noted the authors of the article. “This work introduces EXPERT as a PE tool with significant potential in life sciences.”
The introduction of the EXPERT system marks a progressive leap forward for genetic editing, allowing for more comprehensive and versatile applications. This development could open new pathways for gene therapy and significant advances across various fields including medicine, agriculture, and biotechnology.
With these promising results, the need for future investigations to explore optimizing the system and examining its function across diverse biological contexts becomes clear. The adaptability of the EXPERT system to other prime editing approaches could also suggest potential expansions of its capabilities going forward.
Looking toward the future, with sustained improvements and safety profiles maintained, the EXPERT system stands to revolutionize how researchers approach complex genomic modifications, potentially paving the way for innovative solutions to genetic disorders and other challenges faced across life sciences.