CRISPR-Cas9 technology, often described as ‘programmable DNA scissors,’ has transformed the landscape of genetic research since it first made headlines in 2012. Initially celebrated for its potential in medical science—ranging from creating transplantable pig kidneys to developing treatments for sickle cell disease—its applications in plant breeding are now gaining significant attention. Unlike transgenic plants, which are classified as genetically modified organisms (GMOs) due to the introduction of foreign DNA, CRISPR-Cas9 works by editing the existing DNA within a species. This distinction has allowed it to navigate fewer regulatory hurdles in many jurisdictions, opening new doors for agricultural innovation.
The core mechanism of CRISPR-Cas9 involves designing guide RNAs to direct Cas9 proteins to specific locations in a plant’s genome, enabling precise edits. These edits can include deleting or inactivating genes responsible for undesirable traits. Pairwise, a pioneer in the field, has expanded beyond this basic ‘cutting’ tool to include ‘base editing’ and ‘templated editing.’ These advanced techniques enable the creation of nuanced changes that mimic natural variations. To utilize CRISPR technology effectively, understanding the DNA sequences that control various traits in plants is crucial. Dr. Tom Adams, cofounder and CEO of Pairwise, has spent years studying the natural diversity in domesticated plants’ wild relatives to understand what is possible with CRISPR.
Dr. Adams, a microbiologist and plant scientist with an 18-year tenure at Monsanto, co-founded Pairwise in 2018 with Dr. Haven Baker, Dr. David Liu, Dr. Feng Zhang, and Dr. Keith Young. AgFunderNews recently caught up with Adams to discuss the transformative potential of CRISPR in plant breeding.
“When did it become clear that CRISPR could play an exciting role in plant breeding?” we asked. “It was probably around 2013 or 2014 when I was at Monsanto that it became really clear that CRISPR was going to matter for us,” Adams responded. He noted that while Monsanto’s focus was primarily on corn and soybeans, he saw an opportunity to impact a broader range of crops that people interact with directly. This realization led to the establishment of Pairwise, which secured a $25 million series A round in 2018 and a five-year collaboration with Bayer, investing $20 million annually to build a robust technology platform.
CRISPR’s precision offers exciting possibilities over existing plant breeding tools. Traditional GMO technology has been effective for insect and weed control but struggles with more subtle changes that breeders select for. With CRISPR, modifications are made to native genes in ways that nature has already done in other plant varieties. For instance, if consumers prefer a yellow apple over a red one, CRISPR can mutate a single gene to change the apple’s color while preserving its disease resistance and yield traits.
Moreover, CRISPR can address genetic bottlenecks created by long-term breeding for specific traits like yield. By introducing desired traits from wild varieties without bringing in all 30,000 genes, CRISPR makes the process more efficient. “This ability to not just knock out undesired traits but rather to replicate the variation that nature uses enables us to create the same sort of nuanced changes that occur in nature,” Adams explained.
Pairwise’s gene editing toolbox, known as the Fulcrum platform, includes traditional CRISPR for gene elimination, base editing for small modifications, and templated editing for changing multiple bases. This comprehensive set of tools has made Pairwise an attractive platform for licensing.
Regarding regulatory perspectives, Adams noted that CRISPR is increasingly being treated more like a breeding product than a GMO product. This is because CRISPR works with natural variations within a species rather than introducing foreign DNA. However, debates continue over the extent of genomic edits that can be considered ‘natural.’
In summary, CRISPR-Cas9 technology holds immense potential for revolutionizing plant breeding. By enabling precise, natural-like genetic modifications, it promises to create crops with enhanced traits while navigating fewer regulatory challenges. As the technology continues to evolve, its impact on agriculture could be profound, offering solutions to some of the most pressing challenges in food production and sustainability.