A multiplexed RNA regulation platform for primary immune cell engineering

To overcome current gene editing safety, efficacy, and scope limitations, Stanford researchers in the Mackall Lab and Stanley Qi Lab developed MEGA (Multiplexed Effector Guide Arrays), a versatile and multifunctional platform for programmable and scalable regulation of the T cell transcriptome using RNA-guided, RNA-targeting activity of CRISPR/Cas13d, and successfully enhanced the anti-tumor activity of CAR T cells (see figure 1). MEGA uses molecular scissors to cut RNA, not DNA, to activate reversible changes to gene expression in T cells with expected lower genotoxicity and chromosomal rearrangements compared to CRISPR/Cas9. MEGA is quantitative, tunable, and regulatable without binary changes to genome. It acts quickly and downstream of chromatin remodeling. Researchers demonstrated they could make 10 edits at once to human T cells, compared to 3 with Cas9. MEGA is a safer, more effective, more versatile, and reliable addition to the synthetic immunology toolkit, with many applications in cancer immunotherapy and research.

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Stage of Development

Research - In Vivo: Stanford researchers continue in vivo work to verify the safety and efficacy of the technology, and to enhance anti-tumor activity of CAR T cells.