Small organic molecules underpin modern life, from medicines and flavours to advanced materials. Much of this functional diversity comes from shape: modest changes in a molecule's 3D structure can completely change its properties.
Using CRISPR-Cas9 and adeno-associated virus (AAV)-mediated homology-directed repair, we targeted CAR integration into the endogenous human TCR alpha locus (TRAC). TRAC-CAR T cells display dynamic CAR expression that delays exhaustion and improves tumour control in xenograft and immunocompetent models. This work has been critical for the development of allogeneic CAR T cell therapy, as it disrupts the TCR after transgene insertion—a necessary step to limit graft-versus-host disease.
Central to HR is the RAD51 recombinase, whose assembly into a nucleoprotein filament is governed by five RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3). Mutations in any of these proteins predispose individuals to multiple cancers or genetic disorders. These paralogs are thought to form two functionally separate complexes, BCDX2 and CX3, that act independently at different stages of HR.
GEMINI leverages a computationally designed protein assembly as an intracellular memory device to record the history of individual cells. GEMINI grows predictably within live cells, capturing cellular events as tree-ring-like fluorescent patterns for imaging-based retrospective readout. Absolute chronological information of activity histories is attainable with hour-level accuracy.
Scientists in the laboratory of Rendong Yang, PhD, associate professor of Urology, have developed a new large language model that can interpret transcriptomic data in cancer cell lines more accurately than conventional approaches, as detailed in a recent study published in Nature Communications. Long-read RNA sequencing technologies have transformed transcriptomics research by detecting complex RNA splicing and gene fusion events that have often been missed by conventional short-read RNA-sequencing methods.
Now, researchers have created an artificial-intelligence system that vastly simplifies and accelerates the process of chemical synthesis. The system, which is called MOSAIC and is described in a study published in Nature on 19 January, recommended conditions that researchers were able to use to generate 35 compounds with the potential to become products like pharmaceuticals, agrochemicals or cosmetics without needing to do any further trawling or tweaking.
Biology is undergoing a transformation. After centuries of studying life as it evolves naturally, researchers are now using a combination of computation and genome engineering to intervene, generating new proteins and even whole bacteria from scratch. The use of artificial-intelligence tools to design biological components, an approach known as generative biology, is set to turbocharge this area of research. Just last year, scientists used AI-assisted design to produce artificial genes that can be expressed in mammalian cells.
In the originally published version of this article, Extended Data Fig. 4 contained inadvertent duplications introduced during figure assembly: panel 4c (the bottom of the second column) erroneously reused images from panel 4a (the bottom of the third column); panel 4c (the upper panel of the third column) erroneously reused images from panel 4a (the upper panel of the rightmost column);
Martschenko's argument is largely that genetic research and data have almost always been used thus far as a justification to further entrench extant social inequalities. But we know the solutions to many of the injustices in our world-trying to lift people out of poverty, for example-and we certainly don't need more genetic research to implement them. Trejo's point is largely that more information is generally better than less.
Called AlphaGenome, the model could help scientists discover why subtle differences in our DNA put us at risk of conditions such as high blood pressure, dementia and obesity. It could also dramatically accelerate our understanding of genetic diseases and cancer. The developers of the model acknowledge it's not perfect, but experts have described it as "an incredible feat" and "a major milestone".
