Celebrating Rosalind Franklin’s Centennial with a Nobel Win for Doudna and Charpentier

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The 2020 Nobel prize in chemistry was an exciting and validating event for the genome editing field at large. Perhaps less overtly, it was also a win for women in a year that sorely needed some good news. The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected women with respect to job loss, domestic abuse, and childcare burdens. This year also saw major losses in our fight for access to affordable contraception and a reduction in protection for survivors of college campus sexual assault. Finally, we lost Ruth Bader Ginsberg—perhaps the most notorious of all champions of women’s rights. However, on October 7th, the Nobel prize in chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna, representing the first time, since the establishment of the award, that a science Nobel was awarded to two women and, poignantly, in the same year that we celebrate the centennial birthday of Rosalind Franklin. These two celebrations together provide us all an opportunity to reflect on how far we have come since photo 51, and how much work we have yet to do. What is most uplifting about this year’s award is the collaboration, partnership, and mutual respect between this year’s two laureates that the award brings to the forefront. Partnership and collaboration are something that we particularly appreciate as women working in the genome editing field, a scientific community that, at times, can feel non-transparent, unnecessarily secretive, and uncollaborative. But let this award be a reminder to the community: a rising tide lifts all boats.

The impact of Doudna and Charpentier’s landmark publication¹ describing the mechanistic underpinnings of how the CRISPR-Cas9 enzyme cleaves DNA in a sequence-specific manner cannot be overstated. In only 8 years, this publication has been cited nearly 10,000 times and opened the floodgates for the publication of over 8,000 CRISPR-related manuscripts and the distribution of over 100,000 CRISPR-related plasmids by Addgene. The technology has enabled the submission of 12,000 CRISPR-related patent applications, more than 740 of which have been issued worldwide. Finally, this technology has led to the creation of over twenty CRISPR-based biotechnology companies in the US alone, with more appearing every year. The level of investment in “B.C.” (before CRISPR) gene editing tools pales in comparison.

What these numbers fail to fully capture is how transformative CRISPR has been to the advancement of cell and gene therapy, a field that long pre-dates 2012. While a series of progressive scientific achievements have collectively advanced the field, it seems no single advancement has catapulted the field forward as quickly as CRISPR. The advent of targeted genome editing in the 1990s using meganucleases, zinc finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs) initiated a paradigm shift for cell and gene therapies as scientists were enabled, for the first time, to precisely manipulate the human genome of living cells to achieve a therapeutic effect. However, it is safe to say that CRISPR-based gene editing tools have broadly eclipsed the use of these early instruments. The reasons for the nearly universal adoption of CRISPR-Cas for genome and cell engineering are simple: re-targeting Cas9 to a new locus of choice is achieved using simple Watson-Crick-Franklin base-pairing combined with protospacer adjacent motif (PAM) recognition, and, crucially, the nuclease is highly efficacious in mammalian cells.²

The Nobel committee’s relatively fast turnaround time from initial publication to recognition mirrors the speedy effect of CRISPR-based gene editing on the field of therapeutic genome editing. In 2019, CRISPR Therapeutics enrolled its first patients in clinical trials for the treatment of severe hemoglobinopathies using CRISPR-Cas9 ex vivo cell therapies. While this study represents the first clinical trial in the US that employs CRISPR-Cas as the tool to generate an engineered cell therapy, it is likely just the beginning of the CRISPR revolution across the cell and gene therapy space. Indeed, most recently, Intellia Therapeutics announced the first ever, in vivo CRISPR dosing in humans, representing yet another exciting step forward in this new era of human history and genetic medicine. As more drug candidates, investigational new drug (IND) filings, and clinical trials are disclosed among the numerous gene editing companies feverishly working to find cures for patients, the depth and breadth of the impact of this technology on human medicine will emerge.

Finally, due to the seemingly limitless potential of Doudna and Charpentier’s discovery, researchers have become empowered to focus more time and energy on tackling long-standing, yet previously sidelined, challenges in the field such as delivery, specificity, and precision. Coupled closely with the success of Cas9 as a valuable gene editing tool, investment in innovation on various delivery modalities, including both viral and non-viral approaches, are of particular interest as access to a variety of delivery resources deepens the impact and reach of the technology within human therapeutics for both ex vivo and in vivo approaches. It is certainly not lost on us that the launch of next-generation technologies such as base editing^3,4 and prime editing⁵ were indeed possible because of the CRISPR discovery and that these “CRISPR 2.0” technologies, in turn, broaden the scope of targetable gene correction beyond what was possible with earlier gene editing tools. Fortunately for us all, there are truly incredible and deeply talented people in this field, many of whom are women, working creatively to enable life-long cures for patients suffering from debilitating genetic diseases. And, as scientists whose careers have been bolstered by Doudna and Charpentier’s discovery, we believe the 2020 Nobel Prize in Chemistry was a well-deserved, timely award that would make Rosalind Franklin proud.