This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Genomic editing holds great potential yet continues to have limitations. Current methods either rely on untargeted gene delivery or short DNA edits that need to be individualized for each patient.
A new paper published today in Nature describes a novel genome engineering method called prime assembly that allows long DNA fragments to be stitched into precise, programmable target positions within living cells. This approach may allow for the development of universal gene therapies that can be used for many patients. Prime assembly builds on the techniques of prime editing, an advanced technology that allows for precise yet small insertions, deletions and base swaps.
Because many genetic diseases involve hundreds of different mutations, current gene-editing strategies for a disease might require many different edits to achieve each needed small change. On the other hand, prime assembly could correct DNA with a single approach that could fix almost any mutation in a gene. Prime assembly's single-step process writes new DNA flaps into specific locations in the genome.
The flaps serve as tethers designed to grab DNA fragments with matching ends. The precisely assembled DNA inserts, which can be one or more gene-sized DNA pieces, become large permanent edits. "By using prime editing to write in one flap per strand of the genome, the method controls exactly where the DNA replacement starts and ends," explained Daniel Bauer, M.D., Ph.D., director of the Gene Therapy Program at Boston Children's Hospital and co-senior author.
"Because the method is based on prime editing, it is much less likely to cause off-target effects compared with other gene-editing methods." One such off-target effect is the potential for toxicity. Untargeted insertion methods can turn on the wrong genes in the wrong context, leading to potentially cancerous outcomes, whereas prime assembly's targeted insertion approach circumvents the risk. Prime assembly also does not rely on DNA double-strand breaks or DNA double-strand donors, both of which can be toxic and cause unwanted cell stress.
And while other gene-editing methods are mostly limited to dividing cells, which are rare in the body and more susceptible to unwanted DNA changes, prime assembly works in nondividing cells. Building on this milestone, the team next plans to further investigate the molecular mechanisms that would allow them to engineer even more efficient and precise systems. As they fine-tune their approach, they hope this technology will have a downstream impact in the clinic.
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