COVID-19: BioMaking Solutions - Dr. Pranam Chatterjee, MIT Media Lab, "Computation-Mediated Protein Engineering of Robust Genome Editing and Anti-Viral Tools Against SARS-CoV-2"
Programmable CRISPR-Cas9 enzymes, derived from bacterial immune systems, are powerful and versatile tools for genome editing, with a host of medical, agricultural, and bioenergy applications. To access target DNA sequences, however, they require a short protospacer adjacent motif (PAM) beside the target site, which constrains the total percentage of accessible sequences. To broaden the targeting range of CRISPR, we develop bioinformatic algorithms to discover, characterize, and engineer three Cas9 enzymes from Streptococcus bacterial species with minimal PAM requirements that exhibit optimized genome editing capabilities. These efforts expand the range of CRISPR nucleases from 10% to over 70% of DNA sequences, allowing for targeting of genomic loci that were previously inaccessible, including over 90% of disease-related mutations. Finally, we apply our computational algorithms to develop a peptide-based targeted therapeutic platform for SARS-CoV-2, capable of blocking viral infection and preventing viral replication.