Scientists from ChristianaCare’s Gene Editing Institute have developed an affordable, downloadable app that scans for potential unintended mistakes when CRISPR is used to repair mutations that cause disease. According to a paper published today in The CRISPR Journal, the app, which is called DECODR for Deconvolution of Complex DNA Repair, reveals potentially risky DNA alterations that could impede efforts to safely use CRISPR to correct mutations in conditions like sickle cell disease and cystic fibrosis.

"Our research has shown that when CRISPR is used to repair a gene, it also can introduce a variety of subtle changes to DNA near the site of the repair," said Eric Kmiec, Ph.D., principal author of the study. "We developed DECODR to accelerate the development of CRISPR gene therapies by providing a way to rapidly detect these changes so we can determine whether they pose a risk to patients."  

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The study also presents evidence that the DECODR app, which was written with open-source software, can essentially produce the same data as a deep sequencing process in much less time and at a fraction of the cost. In addition it was reported that DECODR can accurately determine a wide range of insertions and deletions of DNA code that may occur during a CRISPR-directed gene repair to better determine how a CRISPR experiment impacts a targeted gene of interest.    

"We were particularly interested in developing an algorithm that is capable of crunching a large amount of data to break down or 'deconvolute' the outcome of repairs that involve deleting and inserting long strands of DNA code," said lead author Kevin Bloh. "These are edits where there is a greater risk that unintended mutations introduced by CRISPR could disrupt the targeted gene."  

"The beauty of DECODR is that it is designed to be scaled to evaluate insertion and deletions of DNA executed by a CRISPR edit regardless of size," added Byung-Chun Yoo, Ph.D., study author. "This means it can evolve as researchers develop the capacity to attempt more complex repairs."