Leap-In Transposase® platform from ATUM
(please note, this product is currently only offered in US, UK, Europe and China)
The Leap-In Transposase® platform is a comprehensive bioengineered solution for the fast, efficient, stable and robust expression of recombinant proteins in mammalian cells. The platform combines over a decade of vector and gene optimization expertise in conjunction with a novel transposase enzyme. The transposase enzyme is co-transfected as an mRNA along with the DNA expression vectors and transiently facilitates the integration of single copies of the entire synthetic transposon into multiple transcriptionally active genomic loci (integration site TTAA). Expression constructs integrated by Leap-In transposase do not exhibit the typical rearrangements, truncations and concatemerization that are commonly observed problematic hallmarks of classic random integration.
The precise and consistent maintenance of structural integrity of the transposon sequences integrated into the host genome ensures that all regulatory elements remain associated with the appropriate open reading frames, and the desired ratios between multiple open reading frames are maintained.
Importantly, once the transposase mRNA and protein has degraded (24-36hr), there is no cellular enzyme to catalyze the excision of the transposon out of the host genome, resulting in extremely stable integration events
Transposon based expression vectors are designed using ATUM expertise and vast toolbox of technologies in support of the Leap-In platform.
These vectors can be optimised to accommodate multi-subunit proteins and more complex biologics with multiple codon-optimized ORFs with altered expression ratios.
ATUM supports the platform via custom design and provision of vectors for researchers to utilise in-house, alternatively ATUM can perform the transfections and pool generation at ATUM for subsequent cloning at the customer’s laboratory.
Leap-In Transposons offers a simplified and accelerated workflow.
Classic random integration techniques for inserting GOI generally produce only a few high producing clones within a population resulting in the requirement to screen thousands of clones using protein secretion assays e.g. ClonePix, Beacon, Cyto-Mine.
By contrast, using the Leap-In Transposase platform, the majority of the clones from the selected population are high-producers, bypassing the need for high throughput screening. Typically, high expressing clones compatible with GMP scale up can be identified in screening ~100 clones, a process uniquely enabled in as few as 2-3 96-well plates with the VIPS single cell cloning instrument.
In addition, the inherent genetic and productivity stability of Leap-In transposase generated clones allows for subsequent process development and banking without waiting for a separate stability study. As such, stability studies are moved off the critical path for manufacturing clone selection.
Time from transfection to RCB is typically 12 weeks.
Customers interested in this technology should take confidence from the following:
- 10 of the top 20 pharma are licensees, many who are actively moving Leap-In cell lines to the clinic
- One IND filed and accepted by US FDA in 2019
- ~3-4 IND’s expected in 2020
Safe and Stable
Extremely low probability of the transposon coming back out of the genome target
- Efficient and robust integration = Predictable selection
- From transfection to RCB in ~12 weeks
- Integration into transcriptionally active regions = High productivity
- Leveraging > decade of ATUM proprietary vector elements and algorithms
- Highly uniform cell pools up to 5+g/L and clones up to 8+g/L
- Transposase mechanism provides very high clonal genetic stability (takes stability off the critical path)
- No loss in productivity or transgene copy numbers after 90+ doublings
Suitable for Next Generation Biologics
- Compatible with very large inserts (e.g. >100kb)
- Able to co-express multiple genes and tune ratios
- Multiple transposases enable unique genetic engineering strategies
Leap-In Transposase® is a trademark of ATUM®
ATUM offers an integrated pipeline of tools including gene design, optimization and synthesis, expression vectors, and platforms for protein and cell engineering and protein production. ATUM’s tools and solutions are fuelling the transformation of biology from a discovery science to an engineering discipline. By collaborating with clients, ATUM accelerates breakthroughs and moves research further faster. For more information, please visit https://www.atum.bio