Blog July 12, 2017

CRISPR Reaches the Clinic

Sometime mid-month, the first clinical trial employing CRISPR gene editing technology within the human body will initiate in China, at Sun-Yat Sen University. Scientists there will seek to use CRISPR and TALEN, another gene editing method, to treat persistent HPV infection and disable the tumor growth mechanism in infected cells. In a non-invasive approach, scientists will deliver the necessary DNA for gene editing via a gel to the cervixes of 60 women between the ages of 18 and 50.


This trial is distinct from the few previous efforts to use CRISPR therapeutically, which involved extracting cells, treating them outside of the body, and then re-injecting them into the patient with the aim of removing the PD-1 break on the body’s immune response to lung and head and neck cancer. At least 20 additional trials based on this approach are slated to begin over the course of this year and 2018. Most of the planned studies will take place in China and are also focused on various cancers, although CRISPR Therapeutics has a Clinical Trials Application in Europe for a planned 2018 trial aimed at the treatment of beta-thalassemia.


As we have written previously, the aim of CRISPR and other gene editing methods is to be able to readily silence, activate, correct or replace individual genes. The technology has demonstrated enormous value as a research tool, enabling scientists to more easily identify gene function.


As a result of CRISPR’s potential, intense competition and several deals involving big pharma have arisen, including Baxter and Amgen’s participation in Precision Biosciences’ venture financing, and investments by SROne, the corporate venture arm of GlaxoSmithKline and Celgene in CRISPR Therapeutics. Most recently Allergan and Editas announced a $90 million partnership initially aimed at the treatment of a form of hereditary congenital blindness, but also giving Allergan the exclusive right to license up to four additional programs, all focused on rare eye diseases.


The eye is considered to be a good target for gene therapies because genetically altering a few cells can have a significant impact on the disease, with — it was believed — little risk of changes getting outside the eye.  For example, one form of Leber congenital amaurosis, the initial focus of the Allergan/Editas deal, was successfully treated with gene therapy in 2008 with an Adeno-Associated Virus (AAV) vector encoding the RPE65 gene.


And yet, the safety of CRISPR was recently questioned by the publication in Nature Methods of a research study in mice that used the method to correct a gene mutation that caused a form a blindness. The researchers sequenced the whole genomes of several of the treated mice and unexpectedly found small secondary mutations throughout the animals’ genomes in areas not targeted by the experimental therapy. None of these mutations had been predicted by computer algorithms widely used to look for off-target effects. The publication has generated a lot of discussion about the validity of the study, but it has also raised questions about CRISPR’s safety and actual precision.