What makes CRISPR powerful is its ability to target very specific sites in the genome – determined by the guide RNA – and instigate changes based on its “programming.” A huge range of diseases could potentially be treated with the same basic CRISPR machinery paired with mutation-specific guide RNAs. This opens the door to creating a new common regulatory framework with the FDA, and is one of the major goals of our new collaborative project, or Beacon, with the Innovative Genomics Institute (IGI).  
 
Specifically, we’re focused on two rare diseases classified as inborn errors of immunity, or IEIs. As a group, IEIs are fairly common; however, mutations in hundreds of different genes can cause different IEIs, and it is not feasible to run clinical trials for each disease individually. Each patient has a very specific mutation, and the patient might die at six months of age, so we just don't have the luxury of time for standard clinical testing.  

We aim to develop methods for assessing the efficacy and safety of CRISPR-based therapies in a platform fashion – meaning, the same basic approach could be recapitulated across many diseases. We would then work with the FDA to ensure that the approach is safe and appropriate, so that we could help parallel-track clinical development for CRISPR to address a whole range of disease-causing mutations. 

In this collaboration, Danaher’s operating companies provide the means – in the form of reagents, equipment, and analytics – and IGI provides the know-how, the experience, and the authority to work with patients directly.  

For instance, last year at IDT we opened a major therapeutic oligonucleotide manufacturing facility, and we will be sharing our knowledge of how to make high-quality, best-in-class cGMP guide RNAs. We also have expertise in developing Cas9 proteins, including the SpyFi Cas9 that was licensed to Aldevron, which is also part of the Beacon. And IDT will be leveraging our next-generation sequencing platform to screen for off-target profiles in a multiplex fashion, a key step in assessing safety.  

This collaboration involves multiple labs at the IGI as well as several Danaher companies, so good coordination is essential, and I’ll be leading that effort on the Danaher side.  

The goal is to drive innovation and create products that are bigger than the sum of their parts. In industry, we’ve honed methodologies and have hardware and tools that are not always accessible to academics, and we depend on academics for feedback and understanding customer needs. 

In some ways, even though I moved to industry from academia about 8 years ago, I feel like I never left being part of a research group. Our work, particularly in new product development, is very R&D-heavy and we remain close to academics in CRISPR and other high-growth, high-innovation fields. 

There’s a long-running saying in the gene therapy field that also applies to CRISPR in general, and it’s that the three biggest challenges are “delivery, delivery, and delivery.” Identifying the “ZIP code" for targeting cells and getting the therapies to the right tissues in the body, plus having the ability to deliver larger payloads, could open a lot of doors eventually.  

I think we also really need to figure out the genetic variability between different populations and how that may impact efficacy and safety. With the lower and lower cost of sequencing, we have the opportunity to understand biological variation from one person to another, and how it changes during development and with age.  

We also need to be thinking about scaling up. If we want to target indications with much larger patient populations, we will need a more robust and standardized manufacturing process. And of course we have to think about cost and access – now is the time to set the stage for more accessible treatments that can benefit large numbers of people in a wide range of settings.    

Essentially, we need standardization that would allow for quick approvals, an increased likelihood of cures, and a reduction in cost. But we also need to remember that every cell type is different and might require some tweaks to get the right CRISPR “recipe.” If we can achieve both of those goals, CRISPR-based therapies might well someday become a first choice for treating patients.