Manufacturing of Homogeneous T Cells using Synthetic Exon/Expression Disruptors (SEEDs)

Technology Description

Current methods of manufacturing T cells produce heterogeneous mixtures of partially engineered T cells.  Our scientists have developed a one-step process to immunomagnetically deplete non-modified and partially edited T cells, while also reprograming three critical loci encoding T cell specificity, co-receptor expression and MHC expression. This strategy produces 98% purity after selection for individual modifications and up to 90% purity for 6 simultaneous edits (3 knock-ins and 3 knockouts). The method is simple, compatible with existing clinical manufacturing workflows and can be readily adapted to other loci to facilitate production of complex gene-edited cell therapies.

Stage of Development

Characterized editing outcomes and transgene function in cells edited with a single or multiple SEEDs and the ability of SEED-selection to enrich for cells with biallelic integrations in a single step. Demonstrate antibody epitope editing enables enrichment of transgenes and facilitates removal of T cells with mispaired TCRs.

Related Materials

• Ultra-high efficiency T cell reprogramming at multiple loci with SEED-Selection

Patent Status

Additional Patents Pending