Time Magazine recently published the “Time 100“, a list of influential leaders in their respective fields. We are pleased to report that MCB-funded investigator Jennifer Doudna was included as an influential scientist for her transformative research to develop gene editing technology.
Dr. Doudna , along with colleagues and collaborators, developed a now widely used genome editing tool known as the CRISPR-Cas1 system. This invention emerged from Dr. Doudna’s interest in learning how an apparent bacterial adaptive immune system functions on a molecular level that is capable of protecting bacteria from deleterious foreign nucleic acids, including those delivered by bacteriophages. She and others found that CRISPR sequences represent a form of “memory” resulting from previous exposure to foreign DNAs and showed that fragments of these exogenous DNAs are integrated into the CRISPR array. Upon phage invasion, the CRISPR sequence is transcribed, together with a down-stream cas gene that encodes an endonuclease, such as Cas9 in Streptococcus pyogenes. The long, non-coding pre-CRISPR RNA (pre-crRNA) transcript is then processed, producing multiple different crRNAs. The crRNAs form a hybrid to a second CRISPR-encoded RNA called transactivating CRISPR RNA (tracrRNA), which has regions of complementarity to the various crRNAs. These RNA hybrid oligomers associate with the endonuclease and serve as a guide to target newly invading nucleic acids. Recognition of the foreign DNA triggers precise double-stranded cleavage, leading to complete nucleolytic degradation.
Understanding the molecular events by which CRISPRs function on the molecular level led Dr. Doudna and her collaborators to develop the pioneering genome editing capability that functions broadly across many species. Dr. Doudna gives an overview of this technology in the following video.
NSF funding for Dr. Doudna’s groundbreaking research began in 2007 and continues today. Her research represents an excellent example of how fundamental research inspires innovation.
1CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. These repeats are often associated with coding sequences for RNA-guided DNA endonuclease enzymes, general denoted “Cas” for CRISPR-associated.