Broken String Biosciences’ INDUCE-seq platform demonstrates impact of structural DNA changes on specificity of CRISPR-Cas9 gene editing 

  • Research published in Molecular Cell used INDUCE-seq to identify DNA topology as an important regulator of CRISPR targeting specificity 
  • Peer-reviewed data demonstrates the sensitivity of INDUCE-seq DNA break mapping platform, in identifying topology-related off-target events across the genome in cells 

Cambridge, UK, 18 October 2023: Broken String Biosciences (“Broken String”), a genomics company building a technology platform to drive the development of cell and gene therapies that are safer by design, today announced that its INDUCE-seq™ DNA break-mapping technology had been used in a peer-reviewed research paper to characterize off-target effects of CRISPR-Cas9 gene editing resulting from changes in DNA topology1. Published in Molecular Cell, the research highlights DNA topology as a key regulator to CRISPR targeting specificity that must be carefully considered during development of CRISPR-based therapies.  

Since its discovery, the CRISPR-Cas9 system has enabled researchers to elicit precise DNA edits at virtually any site across the genome. However, the full potential of this system as a clinical tool has been constrained by off-target effects.  

The new study was co-authored by a team of scientists, including Broken String co-founders Professor Simon Reed and Patrick van Eijk, PhD. As part of the research, the team analyzed the impact of alterations to DNA structure, in the form of negative supercoiling, on off-target effects of Cas9. Using an adapted cell-free off-target measuring approach, the team identified that negative supercoiling induced up to 10,000 genome-wide off-target events that were formed as a result of increased mismatch tolerance. INDUCE-seq confirmed these findings in gene edited cells, demonstrating that sites of increased superhelical torsion were more susceptible to off-target induction in live cells.  

Professor Simon Reed, Chief Scientific Officer, Broken String Biosciences, remarked: “This study demonstrates the importance of measuring off-target gene editing activity directly in the cells that are being edited. Evidently, there are factors affecting off-target activity in cells, such as superhelical torsion in the DNA structure, that cannot be predicted in silico using DNA sequence analysis alone.” 

  1. Newton, M.D. et al. (2023) ‘Negative DNA supercoiling induces genome-wide cas9 off-target activity’, Molecular Cell, 83(19). doi:10.1016/j.molcel.2023.09.008. 

To learn more about Broken String Biosciences, please visit brokenstringbio.com 

Media Contact

Jake Brown 
Zyme Communications 
E: jake.brown@zymecommunications.com 
T: +44 (0) 7759 162147 

Broken String Biosciences

Moyosola Kara 
Associate Director of Marketing 
E: info@brokenstringbio.com  

NEWS

All News

  • Broken String Biosciences appoints Laurence Reid and Brad Crutchfield to its Board of Directors 

    Broken String Biosciences appoints Laurence Reid and Brad Crutchfield to its Board of Directors 

    Cambridge, UK, 23 September 2024: Broken String Biosciences (“Broken String”), a genomics company enabling development of the next generation of more precise, safe, and effective cell and gene therapies, today announced the appointments of Laurence Reid, PhD, as Chairman, and Brad Crutchfield as Non-Executive Director (NED) of its Board of Directors.  Bringing extensive commercial and leadership expertise to the Board, Laurence…

    Read more

  • Broken String Biosciences appoints Steve Becker as Chief Commercial Officer 

    Broken String Biosciences appoints Steve Becker as Chief Commercial Officer 

    Appointment brings extensive experience to lead commercial operations and accelerate growth in key global markets Cambridge, UK, 24 July 2024: Broken String Biosciences (“Broken String”), a genomics company driving development of the next generation of more precise, safe, and effective cell and gene therapies, today announced it has appointed Steve Becker as Chief Commercial Officer. An experienced global life sciences executive,…

    Read more

  • Broken String Biosciences and the Francis Crick Institute collaborate to advance ALS research

    Broken String Biosciences and the Francis Crick Institute collaborate to advance ALS research

    Partnership to expand applications of DNA break-mapping technology and advance understanding of genomic instability in development of the neurodegenerative disease amyotrophic lateral sclerosis Cambridge, UK,  7 May 2024: Broken String Biosciences (“Broken String”), a genomics company driving development of the next generation of more precise, safe, and effective cell and gene therapies, today announced it has entered a research collaboration with…

    Read more