One of the handful of gene therapy startups has been fine tuning its CRISPR/Cas9 tech in the lead up to taking it into humans.
Building on preclinical work published last summer, investigators at Cambridge, MA-based Intellia $NTLA say they’ve substantially improved on the efficiency of their gene editing work, gaining a 97% reduction in serum transthyretin (TTR) protein driven by 70% gene editing efficiency working in mouse livers. That was with a single IV infusion using its lipid nanoparticle delivery tech. And Cas9 mRNA and guide RNA were undetectable in the liver 72 hours after the infusion.
Last summer, they were working with about an 80% reduction in serum TTR and a 60% efficiency in editing rating.
What’s the big deal about this preclinical work?
By carefully honing its accuracy, Intellia and a group of competitors that includes Editas $EDIT and CRISPR Therapeutics $CRSP want to go into humans looking for a one-time cure with an editing therapy that is quickly flushed, reducing anxieties about any off-target effects that might occur when you release CRISPR/Cas9 in the body.
“We know what gene causes TTR disease and we know that it is the mutant protein made by that defective gene that accumulates in the body and causes the morbidity and ultimately mortality of the disease,” says Intellia R&D chief John Leonard in an emailed response to a query of mine. “When we can knock out the gene that makes the bad protein in mice, it is a good indicator that we can get a similar effect in other animals and possibly people living with the disease. If we can regulate this gene, it can have profound effect on the terrible symptoms associated with TTR. If it turns out that we can do it with a single dose, that will be very important for patients.”
The plan at Intellia now is to do IND-enabling work in TTR in the second half of 2017 and the first half of 2018.
Intellia’s pioneering work helped excite investors last year, helping each of these companies to raise hundreds of millions of dollars through their IPOs. But the bloom is off the rose as some investors calculate the years of R&D work ahead before any new therapies can hit the market.
But they are making progress.
“The fact that we see continuing improvements after a single administration (at least four months) is also noteworthy as it validates the concept of genome editing (i.e., a single edit can propagate to yield continued improvement),” noted Leerink’s Joseph Schwartz.
Intellia’s shares surged 7% this morning, but at about $13 a share, the stock is still well off its $18 IPO price.
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