Spearhead Bio has closed an oversubscribed $1.62 million seed round to advance a genome engineering platform — Transposase Assisted Homology Independent Targeted Insertion (TAHITI) — designed to precisely insert or replace large pieces of DNA at targeted locations in crop genomes.
The round comes a couple of years after Spearhead launched out of Danforth Technology Company (DTC), a subsidiary of the Donald Danforth Plant Science Center in St. Louis, Missouri. The funding will give Spearhead runway to demonstrate how TAHITI can lead to faster and more controlled introduction of genes into both transgenic and non-transgenic crops. Spearhead Bio founder Keith Slotkin says the technology “saves our partners years of development time and millions of dollars in crop improvement.”
How TAHITI works
TAHITI — Transposase Assisted Homology Independent Targeted Insertion — fuses a transposable element directly to Cas9 or Cas12a so that when CRISPR makes a cut, the transposase can insert large genetic cargo precisely into that break. Mike Bielski, CEO of Spearhead Bio, said the company “happens to use CRISPR, but the platform is really about transposable elements and what transposable elements can do with these large DNA cargo movements.” He also said the company is far from being “just another CRISPR company.”
Bielski and the company frame TAHITI as addressing a key limitation of CRISPR: while CRISPR can locate and cut specific sequences quickly, it is “notoriously bad at inserting new genetic material precisely,” often inserting material at random and complicating downstream breeding. Bielski likens this to a paragraph on a page: CRISPR is good at replacing single letters — changing the word “wood” into “food,” for example — but it can’t add or move whole sentences.
Applications and efficiency
According to Bielski, TAHITI enables a new class of large genome edits — rearranging, cutting, and inserting large pieces of DNA — which can be used for stacking traits or complete replacement of genes. “There are so many different things you can do when you have the ability to precisely move large pieces of DNA to where you want them,” he said. Slotkin added that the approach can dramatically improve efficiency for seed companies: “If a seed company wanted to engineer something today, they would have to have this enormous pipeline because the efficiency that they’re working at is below 1%. We can do that much more efficiently, and [the company] can find their desired rearrangement much faster.”
TAHITI can operate in both transgenic (GMO) and non-transgenic applications. Slotkin suggested the non-transgenic route could offer a faster, cheaper regulatory pathway, saying: “Instead of having an additional three years and $80 million to get a trait through deregulation, it’s going to be much faster.”
Partners, milestones and investors
Spearhead is in “active discussions” with partners and is focused on meeting technical milestones, including work on a soybean transposable element and on performing replacements that delete and add at the same location. Slotkin said: “At the same time we’re deleting something, we’re adding something at the same location. So the net balance there is that we’re performing replacements without introducing foreign DNA in a crop genome like soybean with industry partners.”
The seed round was led by BioGenerator Ventures and Danforth Technology Company (DTC), with participation from QRM Capital, Grit Road Partners, St. Louis Port Authority Helix Fund, SDH Capital and other investors. Spearhead Bio is the third company to come out of DTC and, possibly, according to DTC CEO Tom Laurita, “the most impactful new technology to come out of the Danforth Center.” Bielski said the fundraising process “definitely took a while,” but that alignment with the Danforth Center helped “check a lot of investor boxes” and that once investors completed diligence the round became oversubscribed.
