On Tuesday, December 12, 2017, I had the opportunity to meet with a representative from Dr. Feng Zhang’s lab at the Broad Institute. Dr. Zhang has pioneered the development of genome editing tools including those based on CRISPR systems. We discussed some of the exciting research being done in his lab. One area of focus in the Zhang lab is discovering new gene editing systems. One of these systems is Cas13. Unlike Cas9, which targets DNA, Cas13 targets RNA. Some advantages of targeting RNA rather than DNA is that it could be safer in some applications. Since we have only one copy of our DNA, making a permanent change to it using CRISPR/Cas9, would essentially mean that there is no going back. In addition, because Cas9 is not perfect in terms of making cuts in the correct place, it is better to make a change at the RNA, which will degrade, rather than the DNA, which will be there forever.
Another very interesting tool that we discussed is that of Specific High-Sensitivity Enzymatic Reporter UnLOCKing (SHERLOCK). SHERLOCK is a new diagnostic system that can detect extremely low concentrations of viruses in a sample (10-18 M). It can also distinguish between Zika virus and the closely related Dengue virus.
The Zhang lab is also working on a suite of RNA targeting tools. Some of these tools include dead Cas9 and dead Cas13. These tools do everything Cas9 and Cas13 do (target and bind to the DNA or RNA), but they do not make the cut in either. Rather, these tools are used as recruiters for other things such as transcription activators. In addition, GFP can be recruited with a dead Cas13 and used to track transcription. Yet another means of gene editing is that of base editing. Base editing is a good means of editing DNA because it edits the DNA directly and can be done without making a double-strand break in the DNA. Another group at the Broad Institute, run by David Liu, recently reported a new kind of base editor and showed that it could be used to treat deafness in mice.(1)
Another area the Zhang lab is focusing on is neuroscience, specifically neuropsychiatric diseases. The lab wants to create better models to study these diseases by using the tools they have as well as by looking at genetic variants associated with neuropsychiatric diseases. In terms of germline vs. somatic cell editing, the vast majority of diseases can be corrected in somatic cells, eliminating the need to make germline edits. Although this approach substantially decreases some of the ethical concerns about genome editing, a number of important questions remain to be debated. For example, how will the FDA regulate this technology? How will access to this technology be controlled? There may also be disparities in access to this technology, which is likely to be expensive and may be regulated differently in different countries.