Red light penetrates deep into mammalian tissues and has low phototoxicity, but few optogenetic tools that use red light have been developed. Here we present MagRed, a red light–activatable photoswitch that consists of a red light–absorbing bacterial phytochrome incorporating a mammalian endogenous chromophore, biliverdin and a photo-state-specific binder that we developed using Affibody library selection. Red light illumination triggers the binding of the two components of MagRed and the assembly of split-proteins fused to them. Using MagRed, we developed a red light–activatable Cre recombinase, which enables light-activatable DNA recombination deep in mammalian tissues. We also created red light–inducible transcriptional regulators based on CRISPR–Cas9 that enable an up to 378-fold activation (average, 135-fold induction) of multiple endogenous target genes. MagRed will facilitate optogenetic applications deep in mammalian organisms in a variety of biological research areas.

红光可深入哺乳动物组织，光毒性低，但很少开发使用红光的光遗传学工具。在这里，我们介绍了 MagRed，这是一种红光可激活的光开关，由吸收红光的细菌光敏色素组成，结合了哺乳动物内源性发色团、胆绿素和我们使用 Affibody 文库选择开发的光态特异性结合剂。红光照射触发 MagRed 的两个成分的结合以及与它们融合的分裂蛋白的组装。使用 MagRed，我们开发了一种红光可激活的 Cre 重组酶，它可以在哺乳动物组织深处实现光激活的 DNA 重组。我们还创建了基于 CRISPR-Cas9 的红光诱导转录调节因子，可实现高达 378 倍的激活（平均，135 倍诱导）多个内源性靶基因。MagRed 将促进光遗传学在各种生物学研究领域深入哺乳动物的应用。