SAN FRANCISCO (GenomeWeb) – Startup Beacon Genomics is betting that the emerging gene editing market will necessitate services and products that characterize off-target effects, and that next-generation sequencing is the right tool for the job.
Beacon, based in Allston, Massachusetts, launched at the end of 2015 and currently offers two NGS-based services to profile off-target effects of gene editing techniques like CRISPR-Cas9: genome-wide unbiased identification of double-strand breaks enabled by sequencing (GUIDE-seq) and comprehensive in vitro reporting of cleavage events by sequencing (CIRCLE-seq).
Beacon holds an exclusive license for these methods, which were developed in the Massachusetts General Hospital lab of Keith Joung, who is also a scientific cofounder of the company.
Theresa Tribble, a cofounder and head of business development at Beacon, said that the firm currently offers GUIDE-seq and CIRCLE-seq as services. It also plans to develop kits for the methods, which it anticipates commercializing in late 2017 or early 2018.
The GUIDE-seq method was described in Nature Biotechnology in 2015. It works by tagging double-stranded breaks in live human cells using an oligonucleotide. Those regions are then amplified, sequenced, and mapped to identify the location and frequency of off-target effects.
CIRCLE-seq, which was described last week in Nature Methods, is an enzymatic method performed in vitro that can identify off-target mutations associated with cell-type-specific SNPs. Tribble said that CIRCLE-seq is more sensitive than GUIDE-seq, and indeed, in the Nature Methods publication, the researchers found that when used on a single guide RNA targeting the HBB gene that had been previously characterized, CIRCLE-seq identified 26 out of the 29 previously reported off-target sites as well as 156 new sites not previously captured.
The firm's target customers include biotechnology companies with pre-clinical gene editing programs. The goal is to ensure the safety of such compounds by characterizing the off-target effects. A key aspect of Beacon's approaches is that they are genome-wide and make use of NGS, which "provides a very cost-effective and granular look at what's happening in the genome and it allows us to look all across the genome for these potential off-target effects of gene editing," Tribble said.
Tribble said the company is also looking to work with life science tools companies to characterize cell lines that have been edited. The goal there would be to "make sure phenotypes are really caused by the editing and not off-target effects," she said.
Currently, most customers and potential customers have an eye toward the clinical realm, but another potential market is in the ag-bio space, Tribble said, although Beacon has not yet reached out to these customers.
The market for gene editing safety is still new, but Tribble thinks that it will grow quickly as CRISPR/Cas9 is increasingly adopted. Other companies in the field include Caribou Biosciences, which recently described its own method for characterizing off-target effects of gene editing, called SITE-seq, in Nature Methods. Caribou developed the method in collaboration with DuPont Pioneer. The companies have a multi-year collaboration to develop CRISPR-Cas9 technologies in fields that include both human and animal therapeutics, industrial biotechnology, and agriculture.
In addition, Tribble noted that researchers are also developing their own homebrewed techniques for characterizing off-target effects of gene editing. She said that Beacon aims to set itself apart from the competition by focusing on genome-wide methods like GUIDE-seq and CIRCLE-seq. "Our approaches are unbiased and genome-wide," she said. "They don't make an assumption about where those off-target effects will be." In addition, she said, the firm has extensive NGS and informatics expertise, which many of their potential customers may lack.
Going forward, Tribble said that the firm will focus on improving GUIDE-seq and CIRCLE-seq while looking for new techniques to license, especially those that "help to understand not just off-target effects but other types of potential safety concerns." For instance, she said, understanding how the immune system will react to gene editing-based therapeutics would be one important area. In addition, she said that the company will continue to publish data demonstrating the performance of its technologies.
In the much more distant future, when gene editing-based therapeutics begin to be tested clinically, she anticipated that the methods Beacon is commercializing for characterizing off-target effects would also have to be clinically validated. But, she said it is currently too early to understand what the regulatory landscape and requirements would be.