New Online Tool Creates Guide RNAs for CRISPR Gene Editing
By Bio-IT World Staff
March 20, 2015 | Horizon Discovery, a Cambridge, UK-based research supply company with a focus on gene editing experiments, has launched a free online tool to design guide RNA for CRISPR experiments. Horizon, which opened in 2007 providing rAAV vectors for editing DNA in cells, has seen an influx of new types of customers since it began offering CRISPR services.
“CRISPR appeals to people that don’t consider themselves genome experts,” Horizon CTO Eric Rhodes told Bio-IT World. “It was clear that there were a lot of people out there who said, ‘I’ve never done gene editing, but this sounds like something I can do.’”
CRISPR gene editing, derived from a naturally occurring system in bacteria that makes precise cuts in targeted DNA sequences, has led to an explosion of interest in genome engineering since its discovery in 2012. (See also our piece “CRISPR in the Germline,” about concerns that this research is progressing more quickly than scientists can keep up with the ethical implications.) A major reason CRISPR has inspired new scientists to tackle genome editing is that DNA modifications can be directed using RNA molecules, called guide or gRNAs, which are far simpler to create and use than previous targeting mechanisms.
Horizon recently expanded its business to sell gRNAs and vectors for delivering these guides to cells. The company has done most of the design work for these guides in-house, as customers new to genome editing have approached them to create custom guides for specific experiments. Now, Horizon has released gUIDEbook, a platform that automatically suggests new gRNA sequences for human and mouse experiments to remove or insert genes at targeted regions of the genome.
“There are lots of online tools for doing this,” Rhodes admitted, both from companies like Horizon that sell gRNAs, and from academic sources. However, users of these tools have typically switched between programs for different purposes. One program might find appropriate sites for CRISPR cuts in the correct area of the genome; another might try to predict how efficient the CRISPR system will be at producing cuts at these sites; and a third could search the whole genome for similar sites where off-target cuts might occur, potentially confounding experiments. “What we’ve tried to do with gUIDEbook is make it more of a one-stop place.”
No program to date is a perfect predictor of CRISPR activity. “So far, real world predictions are not that great, to be honest,” said Rhodes. “They do need to be checked empirically.” However, tools like gUIDEbook can narrow the field to gRNAs that have the best chance of producing efficient, specific edits, which can then be further selected during early experiments.
Users of gUIDEbook can choose the Wizard mode, for scientists taking their first steps into CRISPR gene editing and looking simply for Horizon’s best suggestions; or the Advanced mode that allows greater customization. In addition to these free online versions of the program, Horizon has also partnered with Desktop Genetics to sell an enterprise version for core labs or pharma companies with greater privacy concerns.
gUIDEbook’s algorithms are based both on an aggregation of public tools, and on Horizon’s own experience designing guides and learning what sequences give the best results. “We had a free CRISPR program that we ran for several months, with the idea of getting lots of reagents out into the hands of academics,” Rhodes said. “We asked them to provide guide performance data back, and we can use that now.”
“I actually think the whole scientific community needs to pull together here,” he added. “We need lots and lots of information on guides in order to really make predictive algorithms that work. But we’re taking our first steps.”
