Xiaojing Gao

@synbiogaolab.bsky.social

Assistant Professor @ Stanford ChemE synthetic biology, biomolecular engineering https://gaolab.blog/

Heading to mSBW? Check out our work brought to you by Connor (Poster 47, genetically encoded urinary reporter to noninvasively monitor live molecular events), JS (Poster 46, efficient biophysical design of orthogonal DNA duplex libraries), and Meng (talk, ablating cancer using RADAR).

Please RT: We're hiring! Computational postdoc for foundation model and sequence-structure-function studies of intrinsic disordered proteins through a consortium and unique large datasets. Ideal candidates have led ML/AI projects in protein design/analysis.

Don't feel bad about missing the mSBW abstract deadline. We have extended it! We also keep the registration fee affordable ($150 for students) so that mammalian synbio-curious trainees can check it out, especially if you are in the Atlanta area. Meeting link below:

We just updated our Germinal preprint for de novo antibody-like binder design! Featuring additional scFv designs, extensive experimental validation of epitope specificity and polyreactivity, and CryoEM structure courtesy of Jim Zhang and Bing Rao from Feng Liang's lab.

Xiaojing Gao@synbiogaolab.bsky.social · 12mo ago

Having often dealt with the frustration of binder-limited projects, we sought a more accessible source for nanobodies than yeast display or llama. Here we introduce Germinal, computationally designing antibody-like binders with such a hit rate that only tens need to be screened for each target.

Have you ever wondered what it would've been like to live in a different kind of society? After a record number of rejections, I'm self-archiving my first attempt at... flash fiction, featuring "Hemingway-esque economy" and "Ishiguro's measured revelation" (if you ask Claude).

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Having often dealt with the frustration of binder-limited projects, we sought a more accessible source for nanobodies than yeast display or llama. Here we introduce Germinal, computationally designing antibody-like binders with such a hit rate that only tens need to be screened for each target.

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We previously built programmable RNA sensors based on editing by housekeeping ADAR enzymes. But they can't sense arbitrary sequences due to design constraints (analogous to PAM for CRISPR). With our new "modulADAR", we overcome that constraint by leveraging ADAR's modularity.

Excited to share our latest: we engineered the reactivity of a bacterial E1-like enzyme for ATP-driven modification of C termini. Our tool mimics the logic of peptide bond formation in biology for precision modification of proteins in vitro. 🧪https://rdcu.be/ewN7C

Engineered reactivity of a bacterial E1-like enzyme enables ATP-driven modification of protein and peptide C termini

Nature Chemistry - In living systems, ATP provides an energetic driving force for protein synthesis and modification. Now, an engineered enzymatic tool has been developed for high-yield, ATP-driven...

rdcu.be

Have you always wanted to take a protein from its native context and make it work elsewhere? Our novel sampler computationally “cytosolize” a secreted enzyme while maintaining its structure, generalizable to other multi-objective guided generation tasks www.biorxiv.org/content/10.1...

ProVADA: Generation of Subcellular Protein Variants via Ensemble-Guided Test-Time Steering

Engineering protein variants to function in exogenous environments remains a significant challenge due to the complexity of sequence and fitness landscapes. Experimental strategies often require exten...

biorxiv.org

Grateful for the recognition and for my team's dedication. When I wrote it in Oct, I didn't anticipate that the title would feel defiant. The original draft even had a now quaint reference to "the comparative comfort of the ivory tower", which was wisely removed.

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So we beat on. Gene/cell therapies would benefit many patients, but often use proteins that could be recognized as non-self by our immune system and cause problems. We combine algorithms to build proteins that are therapeutically relevant and can masquerade as our own parts doi.org/10.1101/2025...

Machine-Guided Dual-Objective Protein Engineering for Deimmunization and Therapeutic Functions

Cell and gene therapies often rely on the expression of exogenous proteins derived from nonhuman organisms. An emerging consensus is to reduce the potential immunogenicity of such therapies by instead...

doi.org

It’s been a tough few weeks. My 10yo daughter was diagnosed with a very rare, aggressive cancer called interdigitating dendritic cell sarcoma (IDCS). I’m reaching out to identify clinicians/patients who have encountered pediatric IDCS or other (non-LCH) dendritic or histiocytic sarcomas cases.

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Proteases might serve as versatile control knobs for gene and cell therapies, but there looms the risk of immunogenicity as we and others have been using viral proteases. We now report a control system based on a an engineered human protease and its clinically approved inhibitor. rdcu.be/d6kVt

Orthogonalized human protease control of secreted signals

Nature Chemical Biology - Engineering of a human-derived protease controlled exogenously by its FDA-approved inhibitor enables control over cytokine activity in cell-based therapies with reduced...

rdcu.be

If you’re feeling too boxed in focusing on one protein, take a journey across the evolutionary tree of life. It’s full of cool surprises. A spider ortholog of my favorite protein sequence, the chromodomain, shares a feature with an enhanced version we engineered. www.biorxiv.org/content/10.1...

An engineered chromatin protein with enhanced preferential binding of H3K27me3 over H3K9me3

The human genome is organized within the nucleus as chromatin, which is largely comprised of histone proteins that assemble on DNA into nucleosome complexes. Histone post-translational modifications (...

biorxiv.org