Roth_Lab

Genetic Technologies and New Gene Design for Curative Therapies
@Stanford - @parkerici - @arcinstitute

[Cell @CellCellPress]

In the latest issue! Synthetic transcription factors designed by domain recombination enhance CAR T cell antitumor function https://t.co/njg3ufc2RJ

[Roth_Lab @Roth_Lab]

This has been a huge effort from Oliver, everyone in the Roth Lab and the Satpathy Lab, and an amazing group of collaborators. None of this type of work is possible without high risk-high reward funding, especially from the @arcinstitute, the @NIH Director ‘s New Innovator Award, and @PICI, @Burroughs Wellcome, and the @Weill Foundation

[Roth_Lab @Roth_Lab]

Transcription Factors are central to cellular identity and function. The human genome currently contains ~1600 of them. But could there be productive human transcription factors that have not evolved? Out today in Cell, a tremendously talented graduate student Oliver Takacsi-Nagy @Oli_TN, together with the @Satpathology Lab, determined to find out. (1/10)

https://t.co/nkzPdF0r0x

[Roth_Lab @Roth_Lab]

Much more functional and mechanistic details about individual top DESynR AP-1 TFs in the full manuscript! But it is exciting to propose that the human genomes natural set of 20,000 genes may not be the only “human” genes that can be productively manipulated when studying human biology, building cellular therapies, or predictively designing optimal genetic perturbations for desired tasks. (9/10)

https://t.co/E6F0wHNXaY

[Ansu Satpathy @Satpathology]

Human protein-coding genes evolved from old parts - reconfigured domains from ancestral genes. We can screen short-sequence evolution at scale using mutagenesis, CRISPR, etc, but we had no way to do the same for domain-level evolution.

Happy to share our work developing DESynR genes today in @CellCellPress: scalable synthesis and functional screening of thousands of new human genes, built from old parts. DESynR transcription factors outperform native factors and dramatically improve CAR T cell function.

A team effort led by the incredible Oliver Takacsi-Nagy! @parkerici @CancerResearch @TheMarkFdn

https://t.co/aMdINxRdAr

[AACR @AACR]

Congratulations to the AACR Trailblazer Cancer Research Grants recipients, supported by @pfizer. AACR’s largest-ever grant program has awarded 15 early-stage and mid-career investigators $1million each to establish novel, highly creative research projects. https://t.co/dXsYggjXmw

[Roth_Lab @Roth_Lab]

Landing pad insertion + recombinase mediated integration is an exciting area! A major difference is the presence of residual scar sequences post integration when using recombinases, as opposed to usually "scarless" HDR mediated integrations. PRIME posted that poster last fall, would be great if they could share more details!

[Roth_Lab @Roth_Lab]

The size of new DNA sequences that can be integrated into the human genome is a foundational constraint for engineering and enhancing human cells. In a new collaborative study, we’ve now almost doubled the maximum size of DNA sequences that can be efficiently inserted into primary human cells.

https://t.co/9Dho2VDbEo

[Roth_Lab @Roth_Lab]

@ProfTomEllis Couldn't agree more - a good rule of thumb is that anything we can do in primary human cells was done ~20 years earlier in yeast

[Roth_Lab @Roth_Lab]

We hope GLIDE-editing may be of use for research and clinical applications requiring integration of ever larger, more powerful DNA sequences into the human genome. None of this is possible without the support of our funders, @theNCI, @NIH New Innovator Award, @arcinstitute, @parkerici, @BWFUND, the Weill Foundation, and the Cancer League (11/11)

[Roth_Lab @Roth_Lab]

This has been a long running collaborative effort, run by exceptional future PhD students Courtney Kernick and Lauren Chow, and an entire team between Brian Shy’s and Greg Allen’s Labs at @UCSF and @GladstoneInst and our group @Stanford and @arcinstitute (10/11)