Intellia Therapeutics has taken another step toward human trials of its gene editing technology after reporting new data in animal models.
The CRISPR specialist says it has been able to show for the first time that it is able to not only achieve long-term suppression of a gene using its gene-editing CRISPR/Cas9 drug, in this case the sequence coding for serum transthyretin (TTR) protein, but also demonstrate a dose-dependent reduction in the activity of the target gene in a second animal species.
New data from studies in mice show that a previously reported 97% reduction in TTR—driven by 70% gene editing efficiency working in mouse livers—lasts for up to six months from a single dose. Meanwhile, a study in rats showed a similar dose-dependent reduction in the TTR gene, and crucially evidence of comparable activity in a second species as Intellia builds the case to move to the clinic.
In this test, a single intravenous infusion resulted in 66% gene editing in the rat liver and up to 91% reduction in serum TTR protein levels. Crucially, the results also backed up earlier data showing the CRISPR drug is rapidly cleared from the body, desirable as it reduces the chances of off-target effects that could cause toxicity. Both datasets were reported at the American Society of Gene & Cell Therapy’s Annual Meeting (ASGCT) in Washington D.C. over the weekend.
Senior VP David Morrissey said the rat study "validates the in vivo CRISPR/Cas9 platform using Intellia's proprietary LNP delivery system," adding that it shows "the ability to expand out studies in larger species.
Under FDA rules, companies typically need data in at least two animal species—including one non-rodent species—before they can progress into human studies. The new data keeps Intellia on course to complete the work needed to get FDA approval for trials of its TTR therapeutic in early 2018.
Companies like Intellia, Editas and CRISPR Therapeutics are vying to bring the CRISPR technology into the clinic, potentially generating one-dose therapies that could cure a host of gene-related diseases, although they will not be the first groups to do so.
Last year, Chinese scientists from Sichuan University's West China Hospital made history when they used CRISPR for the first time on an adult with lung cancer, using cells harvested from the patient that had been genetically modified using CRISPR to remove a brake (PD-1) on the immune response to the tumor. And at the end of April, a second Chinese team from Nanjing University's Nanjing Drum Tower Hospital tested a similar procedure in a patient with head and neck cancer.