CRISPR-Cas genome editing is a highly specific technology that enables edit operations in genomes and other DNA fragments. CRISPR-Cas as a tool in biotechnology is the result of harnessing a similar system that naturally occurs in bacteria. The technology holds promise as a component in therapy and clinical approaches. Indeed - several therapies were recently approved for use in patients. For example - Casgevy, a sickle cell anemia therapy that is showing great positive results. One of the challenges in using CRISPR-Cas technology is the risk of off-target activity - edit events that can occur in undesired locations in the target genome or DNA mixture. In my talk I will present the results of large-scale analysis designed to identify the sequence determinants of CRISPR-Cas12a off-target activity. The data we analyzed is produced by high throughput DNA synthesis. Using several statistical approaches, including the minimum hyper geometric framework (mHG - developed at the Technion in 2007), we are able to point to characteristics of cleavage efficiency based on hundreds of thousands of variants for which activity was measured. All experimental work was done in collaboration with TUM in Munich. By identifying target sequence determinants, our work aims to improve the safety and precision of CRISPR-based applications.
As global data generation grows exponentially, DNA-based data storage technology has emerged as a revolutionary solution due to its high density, stability, and longevity. In the second part of the talk I will describe computational challenges involved in the use of encoding data into composite DNA (work initiated at the Technion in 2016), and solutions to some of these challenges.