thanks!!

I LOVE their curtain test!!

Combining with something like a commercially available AR headset is also probably a good direction - something patient friendly that still allows control over statistics of visual input

Great question, the short answer is no I do not.

There are some avenues here though e.g. coexpress with another less sensitive channelrhodopsin. And I guess if you have to choose between attenuating or amplifying light from the environment, it’s easier to attenuate

But it might be something to do with our transfection protocol - we’ve been hesitant to put too much time into optimizing there since there are many degrees of freedom and we knew just using AAV would solve things

Thanks! I’m fortunate to work with people who will basically run through walls to get data

Re AAV vs lipofection - best guess is that it’s to do with higher and more variable copy number from lipofection; seems like it’s easy to make cells unhappy when lipofecting certain opsins in

Tremendous effort by some very talented people: Amanda Tose, Alberto Nava, Sara McGrath, and @mardinly, among many others

This lowercase science is brought to you by uppercase Science
science.xyz/news/new-fr...

We have a ton of fun details and other results that didn't make it into here, but we'll be dropping more soon.

Please send thoughts/feedback. And holler at us if you want to try WAChRs out for your own experiments, we'll send you some

We also did a low-tech experiment we call the curtain test. It's basically peekaboo: cover the rig with a curtain for a while, then open it again. WAChRs respond pretty well.

Simple - but a sanity check for being able to do something like optogenetic vision restoration.

In particular, WAChRs can drive decent photocurrents with very low intensity light.

We picked three finalists that offer a trade-off between speed and sensitivity: WAChR-f/m/s

We benchmarked these against some existing optogenetic tools on our manual patch clamp rig ("Patchrig Swayze").

We think they offer superior performance for a lot of applications.

We kept Mr. Patchino very busy while we iteratively searched for improvements - several hundred new WAChR variants for this project (and 1750+ so far in our broader campaign).

We ran an ML-guided directed evolution campaign to optimize WAChR. To do this, we developed a system that uses automated patch clamp to quickly screen opsin functional properties.

(We named him Al Patchino)

We used the K+ selective opsin WiChR as a starting point pmc.ncbi.nlm.nih.gov/articles/PM...

WiChR is a strong, sensitive optogenetic silencer. We applied a mutation that breaks K+ selectivity, which converts it into an excitatory channel. We call this mutant WAChR (pronounced "watcher").

Preprint here
www.biorxiv.org/content/10....

Short thread below