Elizabeth Kellogg, Ph.D., standing near the =Krios G4 Cryo-Transmission Electron Microscope. [St. Jude Children’s Research Hospital]
Gene editing tech investments
St. Jude has also made significant investments in novel gene editing technologies. That commitment aligns with Kellogg’s own research on programmable transposons, which have opened new possibilities for gene editing. “St. Jude is a research hospital that has taken a lead in developing new treatments,” she noted. For instance, the hospital has pioneered therapies using gene editing to combat sickle cell disease.
Transposons are a focus area of Kellogg’s research. They are mobile segments of DNA nicknamed “jumping genes” owing to their ability to shift positions within a genome. “They can be extremely useful for genetic engineering and technologies like CAR T-cell therapy.” But their sometimes unpredictable nature can hamper utility. Kellogg’s team aims to tame these jumping genes by developing a new breed of programmable transposons. Kellogg explains, “We became really interested in programmable transposons — transposons that you can actually control where they insert, using an RNA molecule as a guide. A class of transposon studied in the Kellogg lab are the CRISPR-associated transposons. “These were discovered very recently so we’ve been working to understand their mechanism, using use different approaches, from biochemistry to genetics, and of course, structural biology,” she added.
[Learn more about St. Jude’s advanced microscopy-based research.]
Elizabeth Kellogg
Taming jumping genes for targeted therapies
These programmable transposons hold promise for more precise gene editing, offering a way to introduce large DNA sequences into the genome. Kellogg and her team are using the new high-resolution cryo-EM to visualize the workings of transposons. “We applied cryo-EM to really understand how the different components of RNA-guided transposons work,” she said. “And it turns out that they all need to assemble at the target site, but they don’t do it all at once.” Her team can characterize “the whole reaction pathway to determine how each of the components assembles on target DNA. Kellogg’s lab, with backing from the Cystic Fibrosis Foundation, is applying this knowledge to engineer transposons that can precisely insert an intact, functional cystic fibrosis transmembrane conductance regulator (CFTR) gene to correct a faulty CFTR gene, potentially opening up a new treatment avenue for cystic fibrosis patients.
Filed Under: Biotech, Cell & gene therapy, Genomics/Proteomics
