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Orthogonal Inducible Cas13 Platform for Programmable RNA Regulation
Boston University
Gene therapy
Oncology
Pre-Clinical
Abstract
Since its recent discovery, Cas13, a class of RNA-guided ribonuclease, has demonstrated its power in RNA cleavage, editing, sensing, and imaging in various systems. It is a flexible tool for modifying and regulating coding and non-coding RNAs, with enormous potential for creating new cell functions. Compared to other RNA-level regulatory machinery, Cas13 has high RNA cleavage efficiency with little off-target effect, offering a better safety profile of regulation. However, the lack of control over Cas13 activity has limited its cell engineering capability.
Boston University researchers nave developed the CRISTAL [Control of RNA with Inducible SpliT CAs13 Orthologs and Exogenous Ligands] platform which is powered by a collection (10 total) of orthogonal split inducible cell types. This is a powerful platform for precisely regulating RNA dynamics to advance cell engineering and elucidate RNA biology.
Benefits
• Orthogonality, low leakiness, and high dynamic range of our inducible Cas13d and Cas13b
• Engineered Cas13 logic circuits that can respond to endogenous signaling and exogenous small molecule inputs
• Safer and reversible gene expression regulation on the RNA level
• Combinations of our inducible Cas13s can achieve simultaneous multiplexed control of multiple genes in vitro and in mice
• Validated high induced activity in mammalian cells and in mice
• Regulatory mechanism is orthogonal to endogenous cellular machinery and no genome modification required for effectiveness on endogenous targets
Market Applications
• ON/OFF switch for cell-based therapeutics (e.g. adoptive T cell therapy or stem cell therapy)
• Generation of animal models for study of genetic pathologies
• Genetic tools for investigating and manipulating genetic functions
Wilson Wong
US 11572565 B2 (2023.02.07)
Patent Family: US
"Orthogonal inducible control of Cas13 circuits enables programmable RNA regulation in mammalian cells". Ding et al. bioRxiv. Preprint. 2023 Mar 20;2023.03.20.533499
