PNP editing is emerging as a versatile and programmable tool for site-specific DNA manipulations. An innovative genome-editing technique could enhance the delivery, specificity and targeting of gene-modifying tools for treatments.
The KAUST-developed method combines two molecular technologies: a synthetic family of DNA-like molecules known as peptideThe PNAs first unzip and slip inside the DNA helix. The pAgos, guided by short fragments of genetic material, then bind the loosened helix at specific target sequences and nick each opposing strand of DNA.
In many ways, the approach is similar to other gene-editing platforms. However, PNP editing offers distinct advantages compared to more established methods like CRISPR., accurately creating breaks in double-stranded DNA, with fewer chances for off-target activities that could pose a safety risk. "The technology we built significantly improves the efficiency and the activity of programmable double-strand breaks that could be used for gene editing," says KAUST bioengineer Magdy Mahfouz, who led the study.
Further refinements are still required, however, before PNP editing can be harnessed for clinical applications."We need to optimize delivery and demonstrate robust in vivo activity—both in cell-culture experiments and in animal models of disease," says Tin Marsic, a Ph.D. student in Mahfouz's lab and the first author of the research report.
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