Eventually, one could say that the iPhone basically invented the smartphone market with its interactive touch screen, internet surfing capabilities, app store and camera. Except it did not. LG Prada, released in 2006, had a camera, apps, a web browser and the same type of touch screen as the iPhone. LG had the technology right, but another company came together and simply made it better. A similar dynamic can now play out in the world of genre editing.
Although there are three main re-editing tools in use today, CRISPR, which stands for “clustered regular intervals short palindromic repetitions”, has become the most widely used because of its simplicity and versatility. One of the listed companies that uses CRISPR to develop treatments for diseases is CRISPR Therapeutic (NASDAQ: CRSP). Despite acceptance of CRISPR-Cas9 as the standard gene editing system, new methods are being discovered that can turn CRISPR Therapeutics̵
Keep an eye on the ball
Jennifer Doudna, a biochemist at the University of California, Berkeley, and Emmanuelle Charpentier, who headed a laboratory at the University of Vienna, first published evidence that CRISPR could cut targeted DNA in June 2012. But a patent was filed seven months later by the Broad Institute of MIT and Harvard tried to sign the couple’s exclusive claim to commercialize the approach by outlining a more specific description of the process in the cells that make up plants, animals and humans.
Despite the dispute over patents and license revenue, Doudna and Charpentier won the Nobel Prize in Chemistry 2020 for discovering the bacteria’s editing functions using CRISPR-Cas9. Today, Doudna is associated with Intellia Therapeutic (NASDAQ: NTLA) and Caribou Biosciences, while Charpentier is affiliated with several companies, including CRISPR Therapeutics. Another listed company, issued Medicine (NASDAQ: EDIT), was originally founded by Doudna, but is now associated with Broad Institute patent claims.
While the fighting in court continues to this day, other companies are finding new CRISPR tools that, under certain circumstances, can be even more effective at editing nuisances. The basic tool, CRISPR-Cas9, makes a blunt double-stranded DNA break. A disadvantage of this approach is the tendency to occasionally make cuts at unintentional sites in the DNA. Although additional techniques have largely overcome this, it is a frighteningly possible side effect. CRISPR-Cas12 was the next widely accepted tool. This method makes staggered cuts and can edit epigenomes – the chemical compounds that can tell genes to turn on or off. Cas13 affects gene expression by targeting RNA instead of DNA. Recent research, however, has revealed CasX and CasY. CRISPR-CasX is smaller than Cas9 and can be used to control gene expression, not just to edit genes. CasY works a lot like Cas9, but is made of a completely different protein structure, so it can work under different conditions.
New technology trying to skip old technology
In 2017, Excision BioTherapeutics was the first to receive an exclusive license for the new CasX and CasY genre editors from Jennifer Doudna’s laboratory at UC Berkeley. In March, the company used the Cas9 tool to successfully remove simian immunodeficiency virus (SIV) genomes from monkeys. SIV is an HIV-like virus that affects monkeys; removal of the genome of the virus eliminates its ability to infect cells. Excision is also working on gene-based approaches to the treatment of herpes and a rare disease of the central nervous system. And the company uses the CasX and CasY tools for hepatitis B and COVID-19, respectively. Apart from its work on HIV, none of the company’s treatments are expected to start in clinical trials by 2022.
So far, CRISPR Therapeutics is safe. The company’s pipeline is currently targeted at beta-thalassemia and sickle cell disease – diseases caused by a single gene defect, ideal for the Cas9 approach – and multiple immune cell products designed to attack cancer cells. Despite advances in new gene editing methods, even Excision BioTherapeutics relies on the Cas9 tool in most of its clinical trials.
Do not get too comfortable
Investors in CRISPR Therapeutics and other gene editing companies such as Intellia Therapeutics and Edita’s Medicine should not be complacent. When investing, it is easier to understand faster and cheaper technology in computers or consumer products. Just because these advances are in biology does not mean that the same rules do not apply. Researchers will continue to find better and cheaper ways to manipulate genomes to treat and cure diseases. The fact that a small startup managed to grab an exclusive license from the Nobel Prize-winning laboratory that practically invented genre editing should sound alarming. Wise shareholders will look for indications that the CasX and CasY tools are used in areas that were once assumed to be the domain of CRISPR Therapeutics’ and its Cas9 methods.