Selective genetic manipulation of dual-marker expressing target cells using split-effector molecules


Strategy for specific in vivo targeting of marker co-expressing cell types such as bronchioalveolar stem cells (BASCs). Inactive halves of an effector molecule are expressed separately from the two BASC-defining genetic loci (I). Upon co-expression, split-inteins fused to the effector halves (= exteins) re-assemble (II) and perform autocatalytic protein trans-splicing (III), thereby reconstituting a biologically active, full-length effector. Reconstituted effectors enable the selective manipulation of dual-marker expressing target cells, e.g. BASC-specific activation of a reporter gene (IV).

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