Unequivocally, one of the major safety concerns with CRISPR-Cas9 editing, as it’s called, is off-target effects. The CRISPR-Cas9 system is directed to the intended location using a guide segment of RNA with a string of nucleotide repeats that match a patient’s DNA nucleotide repeats at the location of the target gene. A problem arises when there is an identical segment of DNA nucleotide repeats elsewhere in the genome, thereby causing it to be edited at an unintentional location. Even if the intended target gets edited, the enzyme can still continue to cut and edit other off-target segments of DNA. To reduce the probability of this occurring, scientists are using web-based algorithms to calculate the chances that their guide segments of RNA will have off-target binding. Yet there is a major limitation in utilizing these algorithms based on the fact that the DNA used comes from libraries of composite or reference DNA. Since every person has different DNA due to silent mutations and genetic variation, there is a chance a patient will experience off-target effects even though the algorithms suggest they will not. Why is unintentional binding and subsequent off-target effects such a big deal? Well, while an off-target effect may have no impact on a patient whatsoever, it could alternatively have a devastating impact by disabling a tumor-suppressing gene or activating a cancer causing gene. Remember, that regardless of how sure you are that an RNA segment will not have any unintended binding, you can only guarantee that an RNA guide will not bind unintended targets that you are aware of.
Putting the scientific concerns of CRISPR aside, there is also a very intense patent war going on between the University of California, Berkeley and the Broad Institute at MIT with respect to this technology. In fact, both sides are in the process of presenting their case to the United States Patent and Trademark Office (USPTO) to determine who deserves the patent on using CRISPR-Cas9 to edit genes. Since companies have already licensed these patents, they have a vested interest and are willing to spend a lot of time and money to fight it out for as long as it takes to win. Interestingly, rather than an academic battle about who deserves credit for this discovery, the commercial aspect appears to be the driving force behind these filings. Patent issues are not limited to the U.S. federal court, Berkeley is also hitting roadblocks in Europe. Their patents are facing multiple challenges under the European Patent Office’s opposition process due to different nuances in rules revolving around the patent application as compared to the USPTO.2