We’re just a few weeks away from publishing our report on the fast growing market for CRISPR/Cas9 products. In the meantime, we’ve also been engaging with scientists on the ethical questions surround this exciting technology. Before the recent announcement from China that CRISPR had been used to modify human embryos, a slight majority favored such research. Once the story from China broke, we immediately re-fielded the question to a larger group and the pendulum quickly swung the other way.

In parallel to our Instant Poll we also asked the question about human germline editing as part of our broad survey of genomic researchers and their use of CRISPR/Cas9. Here again, we found great excitement about the potential of the technology but a general unease as to whether it is fully understood.

One member of our scientific panel explained it this way:

“Very powerful technology with the capability to improve human health dramatically in the case of some heritable diseases, this should not be ignored. However, the risks associated with these technologies need to be fully evaluated and considered, probably involving long-term animal studies, before regulatory framework can be effectively put in place.”

But another researcher countered:

“The technology exists to prevent horrible heritable diseases from being passed down. Some of these diseases are caused by relatively simple genetic rearrangements or mutations (e.g., cystic fibrosis). Not tackling these challenges is counter to ethos of scientific innovation and progress! I understand the concern for off-target risk and for the ethical debate. Treating disease, I argue, is not up for debate. If off-target effects can be eliminated (or rapidly detected), then why not push the science forward?”

The problem is that because Cas9 induces double stranded breaks, any off target nuclease activity can cause mutations in those genes and possibly lead to unforeseen consequences. For example, off-target mutations in tumor suppressor genes can cause cancer. It’s also been observed that CRISPR/Cas9 can tolerate one to three mismatches in the target which can lead to off target nuclease activity. The potential off-target effects of the Cas9 nuclease represent a major safety concern for any therapeutic application. This will likely remain true until one of our clients develops a reliable and sensitive method to measure the accuracy of CRISPR-Cas9 genome-wide.

In an online Q&A about its GeneArt CRISPR system, numerous questions were asked of Thermo Fisher about the off-target issue. Thermo Fisher pointed out that “By careful designing of crRNA target oligos and avoiding homology with other regions in the genome one can minimize off target-effect.” This could be easier said than done.

Sigma-Aldrich comes at the problem from a slight different angle. Sigma offers an exclusive online design tool that allows users to identify the best target site(s) within human, mouse, and rat protein-coding exons that adhere to CRISPR/Cas9 targeting requirements. The company claims that this is the “only commercial tool that minimizes the possibility of off-target effects by automatically applying CRISPR/Cas9 best design practices.” Other suppliers mentioned in our survey are taking steps to update RNAi reagents to help users address off-target effects.

One thing remains clear, life science suppliers will need to listen closely to the needs of scientists using CRISPR/Cas9 in order to stay abreast of the fast changing competitive landscape. We’re confident our report

Moratorium Human Germline Gene Editing (720x720)The Market for CRISPR/Cas9 Products will be an invaluable resource for any company in the market or contemplating entry.

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