Anti-viral Machinery and Cell Editing Platforms

Nature harbors undiscovered mechanisms of host defense with powerful DNA and RNA targeting capabilities. As an Allen Distinguished Investigator, Jennifer Doudna will explore these new frontiers. 

It is now possible to edit the genome of any organism to obtain desirable genetic changes in individuals or populations. Hailed as the 2015 Breakthrough of the Year by Science magazine, Crispr-Cas9 technology was the outcome of curiosity-driven research conducted by the Doudna and Charpentier laboratories in the United States and Sweden.  Known as Crispr-Cas9 due to its origins as part of a bacterial adaptive immune system, this technology has the potential to cure diseases, improve agriculture, and adapt industrial organisms to produce a wide range of bio-based renewable products.

Editing DNA in human and other eukaryotic cells remains challenging in part because these cells’ genomes are tightly wound around histone proteins in chromatin, creating a physical obstacle to editing many genes of interest.  The team will seek a solution to this hard problem by exploring the many homologues of current editing proteins which exist, including in archaeal systems. By digging into large metagenomics DNA sequencing databases, through the Banfield lab at the University of California, Berkeley, and the DOE Joint Genome Institute, this team will discover new proteins with potential large benefit to gene editing technologies.

Cas9 proteins from archaea— organisms that live in high temperatures or high acid environments—appear to have some unique properties, including the ability to reach currently inaccessible parts of eukaryotic genomes.

There may also be a set of proteins that perform similar functions to Cas9 but do not have a shared evolutionary history or significant sequence similarity. These proteins are thought to be relatively rare, but our expanding dataset of understudied microbial genomes is a favorable setting to discover them.

Even more radical methods for cell editing may become possible through the team’s pioneering exploration of RNA targeting. Achieving new ways to target RNA without genomic DNA manipulations would transform this field of bioscience.

The impact of this work could open entirely new ways to edit cells, understand biological function, and make technology to edit genomes more effective, with widespread benefits throughout the fields of medicine and environmental health.  

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Affiliated Investigators

Jennifer Doudna, Ph.D.

University of California, Berkeley

Jennifer Doudna is the Li Ka Shing Chancellor’s Chair in Biomedical and Health Sciences and she is Professor of Molecular and Cell Biology and Professor of Chemistry at UC Berkeley and an Investigator of the Howard Hughes Medical Institute.  Prof. Doudna’s research seeks to understand how RNA molecules control the expression of genetic information. Her research led to insights about CRISPR-Cas9-mediated bacterial immunity that enabled her lab and that of collaborator Emmanuelle Charpentier to re-design this system for efficient genome engineering in animals and plants, creating a transformative technology that is revolutionizing the fields of genetics, molecular biology and medicine. She is a member of the National Academy of Sciences, the American Academy of Arts and Sciences, the National Academy of Medicine and the National Academy of Inventors. She is a recipient of awards including the NSF Waterman Award, the FNIH Lurie Prize, the Paul Janssen Award for Biomedical Research, the Breakthrough Prize in Life Sciences, the Princess of Asturias Award (Spain), the Gruber Prize in Genetics, the Massry Prize, the Gairdner Award, the Nakasone Prize and the L’Oreal-UNESCO International Prize for Women in Science.