Josh Tycko
@JoshTycko
Followers
2K
Following
19K
Media
107
Statuses
793
Postdoc at Harvard Med, Greenberg lab & BIDMC, Pollak lab aka DJ Fishing Expedition
Boston, MA
Joined March 2014
Our new paper on epigenome editing is out! We mapped which effector domains regulate transcription across genomic, cell type and DNA-binding domain contexts. Then we built new gene repressor and activator tools with improved efficiency & deliverability https://t.co/VqRLtNFey7
nature.com
Nature Biotechnology - Improved effectors for CRISPRi/CRISPRa are developed following high-throughput screening of transcriptional domains.
3
70
361
Programmable promoter editing for precise control of transgene expression https://t.co/6jC9QnVgzn
4
110
470
thank you SPARK for supporting our work in its early days!
@stylus_medicine emerges from stealth to develop in vivo genetic medicines The company was co-founded by Stanford professors, who received funding and support from SPARK https://t.co/kMJ6GQIuFA
0
1
11
The machine-guided humanization paper is out after peer review! https://t.co/wPbHYMDhhV Key contributions from current and previous international students on visas, representing 5+ countries.
So we beat on. Gene/cell therapies often use proteins that could be recognized/rejected as non-self by our immune system. We combine algorithms to build proteins that are therapeutically relevant and can masquerade as our own parts
0
4
27
In a medical milestone, a customized base editor was developed, characterized in human and mouse cells, tested in mice, studied for safety in non-human primates, cleared by @US_FDA for clinical trial use, manufactured as a complex with an LNP, and dosed into a baby with a severe,
44
435
2K
Recombinases are simple short proteins that are sufficient to integrate long DNA with high specificity Combined with simple lipid nanoparticles, this could be a way to make durable cell therapies affordable and distributable
Stylus originated from a wonderful scientific collaboration discovering serine DNA recombinases with Ami Bhatt, @BintuLacra, and @MCBassik spearheaded by star researchers @mgdurrant @AlisonFanton @JoshTycko A huge thanks also to Cosmas Giallourakis and @eminkow for their
0
1
17
So excited for the Stylus team and their progress turning recombinases into therapeutics!
Delighted to publicly launch @Stylus_Medicine today to program the human body into a cell therapy factory to fight cancer. It's a privilege to work with Emile and Jason as CEO/CSO of Stylus and our earliest believers Josh Resnick/Ness Bermingham from RA Capital + @khoslaventures
0
0
11
How Multiplexed Gene Fragments are Expanding What’s Possible in Molecular Biology! @TwistBioscience @JoshTycko Moving Beyond 300 Base Pairs | Twist Bioscience https://t.co/ZVG9GWkxs8
0
10
14
Check out this new preprint showing how to engineer proteins for therapeutics while mitigating immunogenicity!
So we beat on. Gene/cell therapies often use proteins that could be recognized/rejected as non-self by our immune system. We combine algorithms to build proteins that are therapeutically relevant and can masquerade as our own parts
0
1
17
Joining the culture war! We tried liquid culture to re-amplify a lenti sgRNA plasmid library from @Addgene. N=1 but it wasn't worse than our traditional large plate protocol, and seems even better in uniformity and liquid culture is easier to do thanks @nmateyko @CarldeBoerPhD
Do you really need to spread plasmid libraries on mountains of plates to get uniform growth, or can you just dump them in a flask and call it a day? We make huge plasmid libraries in the de Boer Lab, so we tested whether culture method really matters. 1/
1
1
23
Today we report that an engineered skin bacterium, swabbed gently on the head of a mouse, can unleash a potent antibody response against a pathogen. Could lead to topical vaccines that are applied in a cream. @DjenetBousbaine led the charge... @Nature 1/55
15
253
1K
A dream come true: in 2004 I started thinking about counting microstates to predict gene expression with @JKondev Rob Phillips @HernanGGarcia. 20 years later we can measure them: https://t.co/fz6kKAsdpD Thank you @WJGreenleaf @bgrdoughty @MichaelaThinks Julia and all co-authors!
nature.com
Nature - A study uses single-molecule footprinting to measure protein occupancy at regulatory elements on individual molecules in human cells and describes how different properties of transcription...
7
80
461
Incredibly excited that our paper linking single molecule states of TF binding to gene expression using quantitative thermodynamic models is out in Nature today. An amazing collaboration with the Bintu Lab. Congrats to Ben, Michaela, and Julia!
nature.com
Nature - A study uses single-molecule footprinting to measure protein occupancy at regulatory elements on individual molecules in human cells and describes how different properties of transcription...
10
107
513
🧬 Thrilled to share our latest work on engineering precise DNA recombinases for targeted genome integration! Through directed evolution & protein fusions, we achieved over 50% efficiency & 97% specificity for multi-kb DNA cargo insertions. Big thanks to all co-authors -
🧵In new work, we report a systematic engineering roadmap to optimize large serine recombinases (LSRs) for direct, site-specific insertion into the human genome 🧬. We achieved over 50% insertion efficiency and 97% genome-wide specificity, a 10X improvement over our previous work
7
22
131
Development of compact transcriptional effectors using high-throughput measurements in diverse contexts https://t.co/ZELzFp9Ivs
2
26
120
ultimately these large scale measurements will help us to accurately model and manipulate how diverse factors assemble at regulatory elements to produce specific transcriptional outputs
0
0
1
It's an active week for transcriptional effectors! check out these two exciting preprints using dCas9-recruitment of larger combinations of effectors to endogenous genes https://t.co/SwFuEEmScl
https://t.co/micBlEEbFc
excited to share COMET! A scalable CRISPR approach we (@carwils) developed to identify multidomain proteins that modulate transcription at specific endogenous genomic loci. @arcinstitute @ucsf
https://t.co/Qhe38N1zzj
1
0
1
Our plasmids, including NFZ activator constructs, are available on Addgene and we hope they're useful to the community
1
0
1
This project with my tireless teammate Mike Van was another long collaboration between @MCBassik and @BintuLacra's labs, with so many labmates including Aradhana, @nicole_delrosso and our neighboring lab (@stanleyqilab @Xiaoshu625) contributing a ton along the way! Thank you all!
1
0
2
NFZ improves their tunable chimeric antigen receptor T-cell platform (aka SynZiFTR) - it provides more inducible CAR expression and more potency from engineered primary T cells
1
0
3
This project moved across the country with me after grad school - we did revision experiments in my postdoc lab and, most excitingly, started a new local collaboration in Boston with @MoKhalilLab and Belle Ye!
1
0
0