HaleyLab

Our last pre-print of 2024! We created a simple-to-use, temporally-controlled CRISPR/Cas9 toolset that doesn’t compromise between background and induced editing. biorxiv.org/content/10.110…

@Aiims1742 nejm.org/doi/full/10.10… TCR-T, rather than CAR-T. Maybe neoantigens are better than TAAs as solid tumor T cell therapy targets?

Has any CAR-T product ever shown clinical efficacy in pancreatic cancer (besides the occasional transient stable disease). I am not aware of any such example. Please correct me if I’m wrong.

@AdrianoAguzzi Unfortunately not right now. You can request them through the Genentech MTA portal (please reference Andrew Ng, co-last author, in the request): gene.com/scientists/mta

Our last pre-print of 2024! We created a simple-to-use, temporally-controlled CRISPR/Cas9 toolset that doesn’t compromise between background and induced editing. biorxiv.org/content/10.110…

@Ella_Maru Really appreciated your question and interest in the manuscript! We also love your science art!!

@labohaley Thanks for the detailed explanation! This is super interesting and helpful! Keep up the great work!

@Ella_Maru Notes: Some cell lines (SW480) have super high basal activity from the TRE3G promoter. A different promoter/inducer combo might reduce background. Other lines (HCT116) were poorly inducible. Extra control measures reduced background, but with a slight hit to induced editing.

@Ella_Maru Excellent question! General application of inducible Cas9 was a key emphasis of our work. In short, yes, we find the Ultra-tight system will work "best" for balancing induced vs. un-induced editing across cell lines.

We’ve been excited about sharing these fantastic new systems with the community (some of you had a preview at the last CSHL Genome Eng. conf.), and we would love to hear any feedback or answer any questions you might have for us.

The product of a wonderful collaboration across @genentech led by the brilliant duo of Rajini Srinivasan and Tao Sun, with essential guidance from @andrewng_synbio and contributions from many others.

We hope you find this approach as useful as we did, and don’t hesitate to reach out if you have questions or comment!

And, that worked out every bit as hoped! Shown here is one example of a known phenotype (KDM1a/LSD1 depletion = Vim and/or HLA-I upregulation). More examples in the main text and supplement.

Have you been interested combining Perturb-Seq screening with Cas12a’s unique capabilities for multiplexed guide RNA expression? Us too! So, we figured out some useful tricks to make it possible, which you can find in our new pre-print. Short thread below: biorxiv.org/content/10.110…

@dr_alphalyrae @srikosuri Hmmm…I wonder if anyone has gone down that path recently? 😀

@srikosuri I am convinced that starting your career in tech and then retirement job in academia or a national lab is the optimal path.

One of the more visceral things in being surrounded by the tech industry after academia is 20-30 yo are given vastly more responsibility & power, which leads to a diff culture. It maybe even a little too much on the other side (like >40yo are assumed to be out of touch).

Attention gene editors! We are searching for faculty in gene editing (broadly defined) at UC Irvine: recruit.ap.uci.edu/JPF09319

@AlfredoAndere First-hand experience working with Benching in both Industry and Academia: Barriers for getting their software into Industry were high (feature set, cloud security, etc.). Building a brand in Academia was simpler. Trainees would bring their support for it to Industry later.

Huge respect and admiration for Benchling, but I cant take one more vc telling me about their “strategy” of being free for academics and then selling to them once in industry. That was a mistake! Later re-packaged into a cute story that is very hurtful to our ecosystem.