Jüttner, J. et al. Nat. Neurosci. 22, 1345–1356 (2019).
The ability to target, manipulate and record from defined cell types is imperative for understanding neural circuits. However, we are still limited in our ability to target many distinct cell types. To address this shortcoming, Jüttner et al. created 230 adeno-associated viruses that harbored synthetic promoters and a reporter, and conducted a screen in the mouse eye for expression in specific cell types or limited groups of cell types. The researchers identified 32 synthetic promoters that exhibited useful expression patterns. Synthetic promoters that consisted of previously identified cis-regulatory elements with low methylation levels proved to be most successful. Rods, cones, and different classes of amacrine and ganglion cells could be targeted by the synthetic promoter strategy. For additional specificity, the researchers tested an AND gate strategy involving Cre recombinase and a Cre-dependent expression cassette. A subset of the synthetic promoters was also expressed in the macaque retina in vivo and in the human retina ex vivo.