Vertex Pharmaceuticals signed two CRISPR-based licensing deals in January that boost the company’s gene editing portfolio. In one deal, Vertex regains rights to two DNA-dependent protein kinase (DNA-PK) inhibitors that it had originally licensed to Merck KGaA in 2017. Under the new agreement, Merck KGaA, of Darmstadt, Germany, retains rights to use the compounds in oncology and other therapeutic areas whereas Vertex will pursue these molecules in gene editing applications.

DNA-PKs are enzymes that repair double-stranded breaks in DNA. Following CRISPR–Cas gene editing, which creates such double-stranded breaks, DNA-PKs repair them using non-homologous end joining, which directly joins the two ends but may lead to insertions or deletions at the break site. Vertex intends to use the DNA-PK inhibitors to skew the DNA repair in Cas gene editing toward an alternative and more precise repair mechanism that uses a homologous template to restore the DNA sequences.

In cancer, DNA-PK inhibitors could make DNA-damaging agents such as radiotherapy and chemotherapy more effective. One compound that formed part of the deal—M9831 (also known as VX-984)—has completed a phase 1 trial, in combination with doxorubicin chemotherapy in patients with advanced solid tumors.

Vertex’s second January deal focuses on the development of DNA endonucleases as alternatives to the commonly used Cas9 subtype. The partnership is with Arbor Biotechnologies, a small biotech that, also in January, published the identification and characterization of several subtypes of the Cas12 endonuclease.

Vertex already has a CRISPR–Cas gene therapy in the clinic, CTX001, through a 2015 deal with CRISPR Therapeutics. This therapy uses CRISPR–Cas9 gene editing to engineer a patient’s own stem cells to produce high levels of fetal hemoglobin, and is in phase 1/2 trials for sickle cell disease and β-thalassemia. The latest deals suggest that Vertex continues to see CRISPR–Cas-mediated gene editing as an important part of its pipeline.