Keith Slotkin, PhD, first became interested in transposable elements (TE), colloquially known as “jumping genes,” as an undergraduate student. “They just broke all the rules,” he said in an interview with GEN. “They have totally different regulation and inheritance, and they’re highly dynamic.”
In his lab at the Donald Danforth Plant Science Center, Slotkin has studied these genomic elements in depth in plants. What ultimately piqued his attention was the way TEs readily slotted themselves into parts of the genome that had existing cuts. “We kind of joke in the lab that a transposable element can be lazy. It can cut the genome and insert itself, but if something else cuts the genome, it’s happy to go in there,” he said.
That behavior sparked the team’s interest in turning a naturally occurring mechanism into a controllable tool. His group began thinking about ways to take advantage of this natural tendency to make improvements to plants without the use of foreign DNA. Specifically, “how can we take control of [TEs] from an engineering point of view, one at a time, minimize the off-target effect … and insert it into this position in the genome,” he said.
Last year, Slotkin’s lab published a paper in Nature describing an early version of a transposase-based genome editing technology using the CRISPR/Cas system. Building on that foundational work, Spearhead Bio launched this week to commercialize a more advanced version of the technology. Spearhead is one of several companies launched by the Danforth Technology Company (DTC), a wholly-owned subsidiary of the Danforth Center. Its role is facilitating early-stage development of startups based on technologies developed at Danforth Center.
Slotkin serves as the CSO of the new company, which is helmed by Tom Laurita, DTC’s CEO. The company’s list of initial investors includes DTC, Rovaq Ventures, St. Louis BioGenerator, the Helix Fund, Hjelle Consulting Group, and Alta Grow Consulting. Slotkin’s lab also won the 2019 Danforth Center Big Ideas 2.0 competition and received four grants from the Danforth Center’s proof-of-concept fund to develop the underlying technology. Their work was also supported by grants from the National Science Foundation, including funding from the NobleReach Foundation.
Spearhead’s Transposase Assisted Homology Independent Targeted Insertion (TAHITI) technology is designed to enable the integration of genes into both transgenic and non-transgenic crops. As described in the 2024 Nature paper, TAHITI’s predecessor, Transposase-Assisted Target Site Integration (TATSI), leverages the molecular “glue” feature of transposable elements to provide custom “cut-and-paste” genome editing when it is combined with the CRISPR-Cas system. Inspired by CRISPR-associated transposes in bacteria, Slotkin and his team “fused the rice Pong transposase protein,” which is a well-characterized transposon “to the Cas9 or Cas12a programmable nucleases,” the scientists wrote.
Slotkin and his colleagues tested the system first in Arabidopsis before moving on to testing it in soybean. “We’ve engineered the system to control the one transposable element that we want. We can dictate when it moves, how it moves, where it moves,” he told GEN. “It’s essentially two elements that work together.” One expresses the transposase proteins and the other carries the DNA cargo to be inserted. Controlling these components independently is crucial, Slotkin explained, because it allows the protein machinery to be removed after the insertion occurs.
Furthermore, the commercial version of the technology, TAHITI, addresses some of the challenges with the original version, TATSI. “When we published the paper, the key issue was that the transposable element had significant off-target effects,” he said. Over the last year, his group has refined the system to minimize or completely remove those off-target effects in the commercial version. Internal tests indicate that this version is significantly more accurate in its edits as a result of those changes. “You can think of TAHITI as the version two,” Slotkin said, adding that his lab rarely uses TATSi anymore except for comparison purposes.
“There’s a huge variety and diversity of transposable elements,” Slotkin said. For example, TEs comprise over 70% of the corn genome. “We are very interested in taking control of different transposable elements for different opportunities.” Additionally, Slotkin’s group is experimenting with different sized cargos. The largest TEs reported in the 2024 Nature paper were about 8.6 kb, but Slotkin noted that companies it is in contact with are interested in larger cargoes. His group is already doing Internal testing with larger cargoes and the results have been promising, but Slotkin declined to disclose specific numbers at this time.
On the commercial side, Spearhead Bio has started working on projects with some unnamed customers. The company is based in St Louis, where high-impact crops such as corn and soybean are grown and made into various products such as animal feed. AgBio companies that have approached Spearhead so far typically have plants engineered to express a particular trait—virus resistance, for instance—and are looking to do a targeted insertion to encourage the expression of a linked trait, Slotkin said. In most cases, they have already done their homework and they have the product concept in mind, but “lack the technology to efficiently accomplish the product design.”
To help guide development and navigate the commercialization process, Spearhead has secured several veteran plant biotech experts for its scientific advisory board. The members are Larry Gilbertson, PhD, former biotechnology leader at Monsanto and Bayer, Jerry Hjelle, PhD, president, Hjelle Advisors and a regulatory expert, and Jon Lightner, PhD, former vice president of Biotech at Pioneer Hi-Bred International.
The post SpearHead Bio Offers Precise Plant Engineering Using CRISPR-Directed Jumping Genes appeared first on GEN - Genetic Engineering and Biotechnology News.
In his lab at the Donald Danforth Plant Science Center, Slotkin has studied these genomic elements in depth in plants. What ultimately piqued his attention was the way TEs readily slotted themselves into parts of the genome that had existing cuts. “We kind of joke in the lab that a transposable element can be lazy. It can cut the genome and insert itself, but if something else cuts the genome, it’s happy to go in there,” he said.
That behavior sparked the team’s interest in turning a naturally occurring mechanism into a controllable tool. His group began thinking about ways to take advantage of this natural tendency to make improvements to plants without the use of foreign DNA. Specifically, “how can we take control of [TEs] from an engineering point of view, one at a time, minimize the off-target effect … and insert it into this position in the genome,” he said.
Last year, Slotkin’s lab published a paper in Nature describing an early version of a transposase-based genome editing technology using the CRISPR/Cas system. Building on that foundational work, Spearhead Bio launched this week to commercialize a more advanced version of the technology. Spearhead is one of several companies launched by the Danforth Technology Company (DTC), a wholly-owned subsidiary of the Danforth Center. Its role is facilitating early-stage development of startups based on technologies developed at Danforth Center.
Slotkin serves as the CSO of the new company, which is helmed by Tom Laurita, DTC’s CEO. The company’s list of initial investors includes DTC, Rovaq Ventures, St. Louis BioGenerator, the Helix Fund, Hjelle Consulting Group, and Alta Grow Consulting. Slotkin’s lab also won the 2019 Danforth Center Big Ideas 2.0 competition and received four grants from the Danforth Center’s proof-of-concept fund to develop the underlying technology. Their work was also supported by grants from the National Science Foundation, including funding from the NobleReach Foundation.
Spearhead’s Transposase Assisted Homology Independent Targeted Insertion (TAHITI) technology is designed to enable the integration of genes into both transgenic and non-transgenic crops. As described in the 2024 Nature paper, TAHITI’s predecessor, Transposase-Assisted Target Site Integration (TATSI), leverages the molecular “glue” feature of transposable elements to provide custom “cut-and-paste” genome editing when it is combined with the CRISPR-Cas system. Inspired by CRISPR-associated transposes in bacteria, Slotkin and his team “fused the rice Pong transposase protein,” which is a well-characterized transposon “to the Cas9 or Cas12a programmable nucleases,” the scientists wrote.
Slotkin and his colleagues tested the system first in Arabidopsis before moving on to testing it in soybean. “We’ve engineered the system to control the one transposable element that we want. We can dictate when it moves, how it moves, where it moves,” he told GEN. “It’s essentially two elements that work together.” One expresses the transposase proteins and the other carries the DNA cargo to be inserted. Controlling these components independently is crucial, Slotkin explained, because it allows the protein machinery to be removed after the insertion occurs.
Furthermore, the commercial version of the technology, TAHITI, addresses some of the challenges with the original version, TATSI. “When we published the paper, the key issue was that the transposable element had significant off-target effects,” he said. Over the last year, his group has refined the system to minimize or completely remove those off-target effects in the commercial version. Internal tests indicate that this version is significantly more accurate in its edits as a result of those changes. “You can think of TAHITI as the version two,” Slotkin said, adding that his lab rarely uses TATSi anymore except for comparison purposes.
“There’s a huge variety and diversity of transposable elements,” Slotkin said. For example, TEs comprise over 70% of the corn genome. “We are very interested in taking control of different transposable elements for different opportunities.” Additionally, Slotkin’s group is experimenting with different sized cargos. The largest TEs reported in the 2024 Nature paper were about 8.6 kb, but Slotkin noted that companies it is in contact with are interested in larger cargoes. His group is already doing Internal testing with larger cargoes and the results have been promising, but Slotkin declined to disclose specific numbers at this time.
On the commercial side, Spearhead Bio has started working on projects with some unnamed customers. The company is based in St Louis, where high-impact crops such as corn and soybean are grown and made into various products such as animal feed. AgBio companies that have approached Spearhead so far typically have plants engineered to express a particular trait—virus resistance, for instance—and are looking to do a targeted insertion to encourage the expression of a linked trait, Slotkin said. In most cases, they have already done their homework and they have the product concept in mind, but “lack the technology to efficiently accomplish the product design.”
To help guide development and navigate the commercialization process, Spearhead has secured several veteran plant biotech experts for its scientific advisory board. The members are Larry Gilbertson, PhD, former biotechnology leader at Monsanto and Bayer, Jerry Hjelle, PhD, president, Hjelle Advisors and a regulatory expert, and Jon Lightner, PhD, former vice president of Biotech at Pioneer Hi-Bred International.
The post SpearHead Bio Offers Precise Plant Engineering Using CRISPR-Directed Jumping Genes appeared first on GEN - Genetic Engineering and Biotechnology News.