DNA Break-Mapping Technology to Advance ALS Research

UK-based genomics company, Broken String Biosciences, and biomedical discovery institute, the Francis Crick Institute, have partnered up to expand the applications of DNA break-mapping technology and advance the understanding of genomic instability in amyotrophic lateral sclerosis (ALS) (1). The partnership is funded by Francis Crick Institute’s Business Engagement Fund, which is supported by The Medical Research Council to encourage collaborations between the institute and small-to-medium sized enterprises.

The research collaboration, which was announced in a May 7, 2024 press release, will involve the development of novel applications for Broken String’s DNA break-mapping platform, INDUCE-seq. The technology will be used to assess and understand how genome stability contributes to ALS, which is a progressive and debilitating neurodegenerative disease.

“Our research is focused on exploring how cells repair damage to their DNA, and how failures in this process lead to disease. Following exploratory work with Professor Reed, we were keen to collaborate with Broken String,” said Dr. Simon Boulton, principal group leader, the Boulton Lab (DSB Repair Metabolism) at the Francis Crick Institute, in the press release. “We are excited to leverage the INDUCE-seq platform’s unique capabilities in directly measuring and quantifying DNA double-strand breaks, and applying this to deepen our understanding of diseases that have genomic instability as a contributing factor, such as ALS.”

“This collaboration with the Crick Institute is validation of our differentiated approach to DNA break-mapping; enabling our team to support world-leading research with insights provided through our INDUCE-seq platform,” commented Felix Dobbs PhD, CEO, Broken String Biosciences, in the press release. “[The collaboration] demonstrates a fantastic opportunity to apply our expertise across other key research areas to support the advancement of human health. There is an unmet clinical need for effective ALS treatments, as well as strategies for earlier diagnosis that can significantly improve patient outcomes.”

Broken String’s DNA break-mapping platform has already established its capabilities in gene editing, having been used to identify DNA topology as an important regulator of clustered regularly interspaced short palindromic repeats (CRISPR) targeting specificity (2). The results of the study, which used the platform to characterize off-target effects of CRISPR-Cas9 gene editing results and was published in Molecular Cell (3), demonstrated that DNA topology should be carefully considered when developing CRISPR-based therapies.

“This study demonstrates the importance of measuring off-target gene editing activity directly in the cells that are being edited,” said Simon Reed, chief scientific officer, Broken String Biosciences, in a press release (2). “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.”

References

1. Broken String Biosciences. Broken String Biosciences and the Francis Crick Institute Collaborate to Advance ALS Research. Press Release, May 7, 2024.

2. Broken String Biosciences. Broken String Biosciences’ INDUCE-seq Platform Demonstrates Impact of Structural DNA Changes on Specificity of CRISPR-Cas9 Gene Editing. Press Release, Oct. 18, 2023.

3. Newton, M.D.; Losito, M.; Smith, Q.M.; et al. Negative DNA Supercoiling Induces Genome-Wide Cas9 Off-Target Activity. Mol. Cell, 2023, 83 (19) 3533-3545.e5.

Source: Broken String Biosciences