Steven Banik

Our final version of human AGO2 led editing of RNA is out today in @NatureBiotech! Led by @noScandineHere, we got excited by the reduced immunogenic risk and efficacy advantages of using a human-derived protein for non-downregulatory RNA manipulation.

We showed that ALTER had comparable off-target effects to Cas13 approaches, but when the dosage was reduced, very few off-target edits at reasonable editing efficiency. Inspired by @SynBioGaoLab, we performed further predicted deimmunization via the MARIA algorithm.

@SynBioGaoLab While several things remain to figure out in the delivery and guide SAR space, starting from a human starting point could potentially accelerate therapeutic non-downregulatory RNA manipulation approaches, recognized early by @chembioBryan!

Excited our ratiometric transcriptional activation (RTA) work led by @Melissa_Gray234 is out online today @CellCellPress! Measurements determine what we can discover in biology; we use RTA to turn protein abundance changes into amplified signals.

On the horizon, converting changes in protein abundance into programmable outputs could allow both discovery and reprogramming of biology to respond to endogenous signals and cues in new ways. Looking forward to the future of RTA!

This work was enabled by the fantastic community @Stanford_ChEMH @StanfordUChem @StanfordMed, and by collaborators @corsellos and Nathanael Gray!

RT @nchembio: Bronsted-basic small molecules activate GTP hydrolysis in KRAS-Q61 mutants

Excited to see the amazing work that is to come!

I’m excited to share that I will be joining the @UW Biochemistry and the @UWproteindesign as an Assistant Professor in January 2027.

Excited to share @Melissa_Gray234's tour de force work on a new way to sense protein abundance changes. Protein loss has been a defining phenotype for biological, and more recently, small molecule discovery, and we wondered what we could discover w/ greater scale+sensitivity.

Ratiometric transcriptional activation by protein degradation #biorxiv_synbio

We showcased this discovery ability along with @corsellos and Nathanael Gray's lab to find new molecular glue degraders for new targets by multiplexed high-throughput screening of a focused CRBN-engaging IMiD library. Multiplexing and viability was essential for true positives.

@corsellos Overall, RTA hopefully unlocks new measurements at a larger scale, furthers synthetic biology designs and principles, and establishes transcriptional signal amplification for protein degradation events which might enable new types of cell reprogramming.