Sangsin Lee

How can you know if gene delivery in a primate worked? Typically through expensive scans or histology. With @VincentCostaPhd and first authors @sangsin_lee and McKenna Romac we made synthetic markers that monitor gene delivery and Cre-dependent expression with a blood test. PDF👇

Usually serum markers are detected as they are - often hard to detect, long half-life, or with high background that reduces temporal resolution. What if we could modify the markers in vivo so they can better match our needs? Introducing this concept with erasable serum markers.

I am very thankful to @_BrightFocus and their donors, for the grant we received today. Using these funds we will enable monitoring of gene expression in the intact retina to understand the molecular basis and progression of age-related macular degeneration and improve diagnosis.

qPCR can measure expression of virtually any gene... in homogenized tissues. Here, we show an "in-vivo qPCR" equivalent, where we measure a sequence-specific transcript with synthetic serum markers and enzyme-based signal amplification. biorxiv.org/content/10.110…

Could one envision a synthetic receptor technology that is fully programmable, able to detect diverse extracellular antigens – both soluble and cell-attached – and convert that recognition into a wide range of intracellular responses, from transgene expression and real-time fluorescence to modulation of innate cell behavior (excitation or inhibition of neurons, induction of cell migration, etc.)? Today we report in Nature a new technology platform that provides a step in that direction: PAGERs, for Programmable Antigen-gated G protein-coupled Engineered Receptors, convert recognition of extracellular soluble or cell-attached antigens into diverse user-selected responses. PAGERs are based on G-protein coupled receptors (GPCRs), which themselves are not structurally modular, but we were able to build in modular antigen gating by fusing an antagonist peptide to the extracellular N-terminal end, and then gating the antagonist with a fused antigen-binding nanobody.  When antigen binds, it sterically interferes with the antagonist, leading to relief of receptor inhibition. Drug or agonist can then turn on PAGER. nature.com/articles/s4158…

Absolutely true

2/3 of Korea will disappear every generation. Population collapse.

I am looking forward to coming back to @MIT for Neurotech 2024 tomorrow! I will talk about noninvasive interfacing with the brain, including new projects with our postdoc Sho Watanabe @alfort_123 and collaborators @VincentCostaPhd and Rui Chen (UCI). neurotech.mit.edu

Published today in @Nature, we describe an approach for single-molecule protein reading on @nanopore arrays. By utilizing ClpX unfoldase to ratchet proteins through a CsgG nanopore, we achieved single-amino-acid sensitivity. nature.com/articles/s4158…

How could we check if a gene therapy reached the desired brain region? Here, we noninvasively measure gene delivery and endogenous gene expression in specific brain sites with ultrasound-released synthetic serum markers. science.org/doi/10.1126/sc…

🧬 🧠 Exciting news from Rice BIOE @JerzySzablowski team! Their innovative gene therapy method could revolutionize brain disorder treatments by targeting specific regions with unprecedented precision. Discover more in Nature Communications! news.rice.edu/news/2024/rese…

Can AAVs be evolved for better brain delivery after targeted ultrasound insonation? We report new AAVs optimized for focused ultrasound BBB opening. Congratulations to all involved! @Richieli_Biomed @ManwalHarb John Heath @JakeSTrippett @mikhailshapiro nature.com/articles/s4146…

A team led by the Ajo-Franklin group’s very own @Bacterioman99 has uncovered the mechanism through which E. coli utilizes redox shuttles for extracellular respiration and growth, showcasing the unexpected versatility of microbial metabolism biorxiv.org/cgi/content/sh…

Precisely

We are recruiting! Open projects related to enzyme engineering, protein directed evolution, computational protein design, spatial proteomics, RNA tools, protein therapeutics, and molecular technology development for cell biology and neuroscience. We especially welcome trainees with backgrounds in chemical biology, machine learning, enzyme biochemistry, and molecular biology to join our team! We value diversity and aim to foster an inclusive and supportive environment for trainees. Please reach out to ayting@stanford.edu to learn more!

Neurons and astrocytes closely coordinate their gene expression, in a program we call “SNAP” – a collaboration that we find to be central in protection from schizophrenia and cognitive aging. nature.com/articles/s4158…

⚡️🧠Thrilled to share our new preprint on pain-related valence cell-types + circuits — A nociceptive amygdala-striatal pathway for chronic pain aversion Check out the stellar work of Jessica Wojick, in a co-senior collab with @KorbLab biorxiv.org/content/10.110… THREAD 1/13

Consumers in the United States can now pre-order a genetically engineered plant for their home that glows continuously go.nature.com/3I1fjnm

I'm looking forward to visiting @RiceUniversity on Tuesday! I'll be chatting with faculty and students and giving a lecture on "Exciting Trends on Machine Learning". eventbrite.com/e/ken-kennedy-…

DNA writing tools have revolutionized genome editing but how do we make any possible edit, insertion, or deletion in RNA safely? Today we report on a novel RNA writing tool, PRECISE editing, that allows you to make any edit in RNA. w/ @jgooten 🧵👇🏼 biorxiv.org/content/10.110… 1/18