Engineered CAST systems for RNA-guided DNA integration
This technology is a method for programmable DNA integration in mammalian cells via engineered Cas8 variants within CRISPR-associated transposase (CAST) systems, improving integration efficiency and expanding the range of genomic insertion sites.
Unmet Need: Efficient, programmable DNA integration without double-strand breaks
Current approaches for DNA insertion in mammalian cells rely largely on viral vectors or depend on DNA double-strand breaks for genome editing, both of which are limited in targeting flexibility, efficiency, and genomic safety. Viral methods are constrained by payload size and integration bias, while double-strand break-based editing depends on host repair pathways that are inefficient and susceptible to errors. These limitations limit genome engineering and hinder broader therapeutic applications, underscoring the need for more controlled and predictable DNA integration strategies.
The Technology: Programmable, break-free DNA integration platform in mammalian cells
This technology enables targeted DNA integration in mammalian cells by engineering components of an RNA-guided system through mutations in Cas8 at the proto-spacer-adjacent motif (PAM)-interacting region. Modifications to this region alter target recognition behavior, enabling the integration machinery to access genomic sites that are inefficiently addressed by existing approaches.
This technology has been validated with mammalian cell lines.
Applications:
- Stable genetic engineering of mammalian cells for research and cell line development
- Targeted gene insertion for gene and cell therapy
- Synthetic biology and genomic engineering platform
Advantages:
- Programmable, site-specific DNA integration platform for mammalian cells
- Reduces reliance on double-stranded breaks and host repair pathways
- Expanded genomic targeting flexibility compared to existing RNA-guided systems
Lead Inventor:
Patent Information:
Patent Pending (US 63/592,040)
Related Publications:
Tech Ventures Reference:
IR CU24123
Licensing Contact: Cynthia Lang