CB Insights’ Game Changers 2020 report features three biotech companies under the CRISPR 2.0 category. The report describes CRISPR 2.0 as a system allowing “safer and more precise approaches to gene editing.” Since CRISPR-Cas9 was first described in 2013, scientists utilized other Cas enzymes (e.g., Cas13) and/or tweaked them (e.g., dCas9 or Cas9 fused with another protein) to make more precise edits and expand the types of edits and targets. So, what is special about the three selected biotech companies? Looking into them, I noticed one common theme.
They all aim to target RNA.
1. Why do we want to make changes to RNA, instead of DNA?
As a molecule that transmits the genetic information in DNA to proteins, RNA is present in the cell transiently (it pains me to describe RNA this way and this way only; it’s my favorite molecule and I could talk about it for hours). Therefore, unlike changes in DNA that become permanent, edits in RNA will be effective only as long as the edited RNAs are around. Don’t we want a permanent fix? The answer depends on what you want to achieve with the edits. For instance, if you want to alleviate your pain, you want to do it transiently, not permanently. In this case, you could theoretically use RNA-targeting CRISPR to cleave RNAs of the genes that allow you to feel pain via CRISPR and become insensitive to pain for some time. Moreover, given that the CRISPR system could make changes at unintended sites (aka off-target effects), transient editing through RNA targeting could be safer, leaving no long-lasting, possibly detrimental mutations.
2. What are some challenges to RNA-targeting CRISPR therapeutics?
When it comes to injecting foreign genetic material—whether it’s mRNA vaccine, gene therapy, or CRISPR—finding an effective delivery into the cell and determining a proper dosage become a hurdle to overcome. A challenge specific for RNA-targeting CRISPR, but not DNA-targeting CRISPR, is possibly triggering an immune reaction. While DNA-targeting CRISPR requires a brief presence of Cas (the enzyme that makes a cut in DNA) in the target cell because it just needs to cut a single gene in the genome, RNA-targeting Cas needs to stay in the cell longer in order to make changes to all the target RNAs. Cas enzymes in CRISPR are from bacteria, therefore sustained presence of RNA-targeting Cas could stimulate an immune response.
3. What’s next?
All three biotech companies in CB Insights’ report are focusing on developing therapy for genetic diseases. Another possible avenue for RNA editing is a treatment for diseases caused by RNA viruses, such as influenza viruses, although I don’t know whether RNA-targeting CRISPR therapeutics is better than RNA interference. By inserting RNA-targeting CRISPR components into the genome like GMO, we could also create plants that are resistant to viral diseases.
4. My last two sentences
RNAs do not stay in our cells long, but biotech and pharmaceutical startups’ interests in RNA are here to stay. I’d be very interested in seeing how various RNA therapeutics (e.g., RNAi, RNA editing using ADAR, RNA-targeting CRISPR) as well as the delivery system for RNA develop further.