keeping up with krispr
The most important news in healthcare: Friday Oct 1st
Today, we’re delving into the world of CRISPR-Cas9. Once a theoretical test tube trick, the gene editing technology has increasingly become a reality of clinical medicine. Between the very public patent battles, the number of spinout companies, and the clinical trials, it can be hard to keep up with all things CRISPR. Read on to stay up to date with the latest news this week out of Feng Zhang’s company, Editas, which has been working to cure a form of congenital blindness.
Today’s Pulse is 800 words, or a 7 minute read.
If you like what you read, make sure to drag the email to your “primary” tab!
PHARMAIn vivo CRISPR gene editing for blindness
The pulse:
Editas Medicine just released early clinical data for its CRISPR gene editing treatment for vision loss. This comes on the heels of the first ever successful in vivo CRISPR gene editing study run by competitor Intellia. The Editas data are mixed but could point to future success.
Can we back up a minute for a quick CRISPR refresher?
CRISPR-Cas 9 is a gene editing system that was first discovered in bacteria as a mechanism for attacking invading viruses. Over the past two decades, scientists around the world have discovered it can also serve as a way to edit human genes.
The system works by using a small piece of RNA that can be targeted to any sequence of DNA desired (e.g. a faulty gene in someone with a genetic disease). The RNA guides the CRISPR-Cas9 complex to the gene, at which point the Cas9 enzyme can get to work. Cas9 can be thought of as a genetic scissor that can cut up DNA. In this way, the target gene can either be excised entirely, or replaced with a “fixed” sequence.
CRISPR-Cas 9 system. Source: Noonan Syndrome Awareness Association
The major players:
There are a LOT of CRISPR pioneers, a point that has become hotly contested, in fact. Emmanuelle Charpentier and Jennifer Doudna were awarded the 2020 Nobel Prize in Chemistry for developing the genome editing technology, but it was Feng Zhang of the Broad Institute who successfully obtained the first CRISPR patent. It’s all so complicated, we could honestly write a book about it (but Walter Isaacson beat us to it and if you haven’t read The Code Breaker yet, get on it).
The latest CRISPR-Cas 9 update:
Just this week, Editas Medicine released preliminary data for an in vivo (meaning in the body, not a test tube) CRISPR gene editing study for a rare condition called Leber congenital amaurosis (LCA). LCA is caused by a very specific mutation in the CEP290 gene, making it the perfect target for a technology like CRISPR-Cas9, which can precisely excise the one error sequence that causes degeneration in ocular photoreceptor cells.
Editas tried their experimental treatment in five adult patients with LCA. According to the company’s representatives, two patients in the mid-dose cohort showed some improvement in visual acuity, stimulus testing, and/or mobility navigation. One patient had an improvement of her vision from 20/8,000 to 20/2,500 six weeks after receiving the treatment. The other patient did not have any change in visual acuity but had an improvement in her perception of low levels of white and colored light.
More importantly, there were no serious adverse events noted in any of the study participants. Editas Chief Medical Officer Dr. Lisa Michaels said:
“The first and foremost conclusion on this is that we’ve been able to demonstrate, at least to date, that … CRISPR/Cas9 editing to the back of the eye is so far safe, and that was not known when we first started the study”
Most are not so impressed.
Still, one patient had no improvement in vision at all and another had not been treated long enough to collect data. Given how small the study is, many are wondering if the perceived improvement in the other two patients is just background noise. Editas’s shares were down 19% after the data were announced Wednesday. Another factor playing into Editas’s underwhelming results is the better data from rival Intellia for its CRISPR treatment of a disease called ATTR amyloidosis back in June.
For background, Editas was initially founded by a number of prominent scientists, including Feng Zhang and Jennifer Doudna. However, in 2014, Doudna left the company over suspicions that she was being left off of CRISPR patents and intellectual property (turns out she was right). Still, it worked out pretty well for her. She went on to co-found Intellia, which beat Editas to the punch – Intellia was the first company to release positive data for in vivo CRISPR-Cas 9 gene editing back in June of this year. In comparison, the Editas data doesn’t look quite as hot.
Editas has ongoing studies with higher doses of the treatment and has plans to begin enrolling pediatric patients in the studies, who may benefit more as children have more functioning photoreceptors. Whether that data will be more impressive remains to be seen. In the meantime, Editas can count on its rival CRISPR companies to keep competition stiff.
Bottom line it for me:
In the latest CRISPR tussle, the point goes to Doudna and Intellia over Zhang and Editas following the lukewarm data from Editas earlier this week. Still, we’ll keep our eyes peeled — with CRISPR, the scoreboard is ever changing.