Crispr Cas9 Gene: Broken String Biosciences has made a significant contribution to the field of genomics with its innovative INDUCE-seq™ DNA break-mapping technology. This technology has been utilized in a peer-reviewed research paper, recently published in Molecular Cell, to delve into a crucial aspect of CRISPR-Cas9 gene editing – the impact of DNA topology on its precision.
The CRISPR-Cas9 system has revolutionized genetic research and gene editing, allowing scientists to make highly specific changes to the DNA of organisms. However, one persistent challenge has been the occurrence of off-target effects, where the Cas9 enzyme inadvertently edits DNA at unintended locations, raising concerns about the safety and accuracy of gene editing.
In this groundbreaking study, a team of researchers, including Broken String’s co-founders, Professor Simon Reed and Patrick van Eijk, PhD, investigated how alterations in DNA structure, specifically negative supercoiling, affect the accuracy of Cas9 editing. They employed a specialized cell-free off-target measuring approach to assess the impact of negative supercoiling. The results were eye-opening, as they revealed that negative supercoiling could induce up to 10,000 off-target events across the genome due to increased mismatch tolerance.
To further validate these findings in real-world scenarios, the team utilized Broken String’s INDUCE-seq technology on gene-edited cells. The results provided additional confirmation that sites with increased superhelical torsion were more susceptible to off-target effects in living cells. This research is pivotal in understanding the nuances of DNA topology and its influence on the precision of CRISPR-based therapies.
In essence, Broken String Biosciences’ INDUCE-seq™ DNA break-mapping technology has unveiled a previously underexplored aspect of CRISPR-Cas9 gene editing, shedding light on the importance of managing DNA topology to enhance the specificity and safety of this revolutionary technology. This research serves as a critical step forward in the development of more accurate and reliable gene therapies.
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