Danaher, IGI, CZI Unite for CRISPR Breakthroughs

In January of 2024 we launched an initiative between the IGI and Danaher that I believe will make significant strides toward addressing these hurdles called the Danaher/IGI Beacon for CRISPR Cures. The goal is to create a new platform framework for the development and regulatory approval of CRISPR therapies taking advantage of their modularity. In an ideal future, physicians diagnosing patients with monogenic diseases, for example, would be able to seamlessly determine eligibility for a gene-editing treatment and initiate therapy development with minimal complexity. The vision is to create a modular, plug-and-play framework in which doctors can select from a pre-approved menu of CRISPR editors and delivery vehicles that have been optimized and validated for safety, quality, and manufacturing consistency, and pair them with a personalized guide RNA tailored to the patient's specific mutation. To enable this, we are working toward a regulatory paradigm that decouples the approval of platform components, such as editors and delivery technologies, from the individualized guide sequences. Once a patient is identified, the only variable requiring review would be the guide RNA, which would undergo rapid, standardized safety and quality assessments. This approach would dramatically reduce development timelines and make it potentially feasible for clinicians to incorporate genome editing into routine care for eligible patients. This framework would allow us to create therapies like the one for KJ both efficiently and safely. The Beacon is focused on a set of rare diseases known as Inborn Errors of Immunity, or IEIs, and in particular, two of the most severe forms, familial hemophagocytic lymphohistiocytosis (HLH) and Artemis-deficient severe combined immunodeficiency (ART-SCID). This work will be a model for expanding CRISPR to other disease areas, such as Inborn Errors of Metabolism, like what KJ was born with.

Our collaborator Fyodor Urnov at the IGI often refers to this Beacon as creating a CRISPR Cookbook, and that metaphor works well because what we're building will have both the lists of ingredients (i.e. the reagents, equipment, etc.) and the recipes (i.e. the standardized protocols) needed to make a CRISPR therapy safely and effectively. Since there is so much customization needed to create these medicines, there will also be instructions for how to combine elements to tailor a treatment to a particular patient's needs. The necessary standards and benchmarks will be baked in to these recipes, ensuring work is carried out at the highest quality. Lastly, we believe that this cookbook will help expand access as it will be a shareable resource, democratizing this knowledge and bringing much needed therapeutic options to patients facing life-threatening diseases.