Sickle Cell Disease (SCD) is one of the major targets for CRISPR-based therapies, as it is a heritable disease that affects a patient’s red blood cells to a degree where more of the blood cells become dysfunctional. Despite the current treatment option for SCD, patients have a significantly shorter life expectancy and must manage their entire lives with therapies focused on mitigating the SCD effects.
In 2021, several clinical studies demonstrated the potential for CRISPR to correct the DNA level root cause of this devastating disease. These studies made CRISPR’s revolutionary potential clear to many. Still, at the same time, it also became clear to CRISPR experts that unless new and better ways of getting consistent and reproducible CRISPR results is achieved, CRISPR’s ability to live up to its potential will be limited. This highlighted the need to develop CRISPR Quality Control standards.
“CRISPR-based therapies have been advancing so quickly to combat debilitating diseases such as sickle cell disease, but still, no one fully mastered this new type of therapy yet,” said Aran. “It is simply not precise enough as we do not have a lot of insight or control of what CRISPR does step-by-step, and that may result in unwanted editing the wrong places in people’s DNA with unknown clinical outcomes.”
One of the significant challenges in expanding knowledge and understanding of CRISPR therapies is the lack of standard processes to monitor the quality of reagents and methods to predict better and optimize the outcome.
“I believe there are some critical checkpoints that can be developed to improve the editing outcome and to eliminate CRISPR designs and versions that are not appropriate to be used for patients,” Aran said. “And even if you are just researching cell lines, these standards will with time be able to save a lot of otherwise wasted efforts and resources.”
The Aran Lab has dedicated years of research in understanding CRISPR at a deep level using Cardea BPU technology. As the developer of the CRISPR-ChipTM and its associated applications, Aran has shown the ability to measure how CRISPR operates in real-time. This includes identifying where editing problems may occur, where there might be a need for CRISPR assay optimization, and in more general terms, how to develop Quality Control standards for the use of CRISPR.
This NIH grant is given to further the development of CRISPR Quality Control tools and procedures that will empower tomorrow’s clinicians to deploy CRISPR as a safe, effective, and predictable cure to genetic disease.
“Having tools and assays to characterize and evaluate the quality of genome editing reagents and processes will be very valuable to support confident use of the genome editing technologies,” said Dr. Samantha Maragh, the Leader of the Genome Editing Program at the National Institute of Standards and Technology.
Aran supports Maragh’s sentiment.
“Having CRISPR Quality Control standards and tools that correlate the quality of assay reagents with CRISPR’s performance and the editing outcome will greatly enhance our understanding and expand the safe utilization of CRISPR therapies,” Aran said.