RNA-Based Reprogramming
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RESEARCH HIGHLIGHTS STEM CELLS RNA-based reprogramming RNA molecules can both induce pluripo- RNA-based technique instead of viral tech- development, began producing myotubes. In tency and direct differentiation. niques for much of its induced pluripotent fact, Rossi expects that techniques using RNA The ability to make person-specific pluri- stem cell production. for differentiation will probably be adopted potent stem cells opens up many possibilities Getting the technique to work required more quickly than using RNA for reprogram- for research tools and perhaps even therapies. a lot of trial and error, says Rossi. His first ming. “I think people will have an easier time But most reprogramming techniques alter cells’ attempts to reprogram cells with RNA failed in differentiation because it’s often one factor genomes, making cells less predictable and more because cells responded as if they had been rather than several,” he says. prone to cancer-like growth. Methods to repro- infected by a virus, committing apoptosis or Making the modified RNA itself is easy, gram cells without changing their genomes launching other antiviral defenses. Swapping says Rossi, but researchers will need to exist but are inefficient and labor-intensive; out two nucleosides with similar analogs mit- spend some time tinkering to find the best most also rely on DNA and so still carry the igated the response and allowed the research- conditions for their systems. Every aspect risk of unintended genetic alterations. ers to reprogram cultured human cells by of culture conditions affects how cells are A reprogramming technique recently applying daily doses of RNAs coding for four transfected with RNA, he says. “Whenever reported by Derrick Rossi of Harvard to five pluripotency genes. The extent of pro- a new cell type is approached, everything University uses synthetic RNA molecules and tein expression depended on the amount of needs to be optimized.” eliminates the chance of unwanted genetic RNA delivered, offering the researchers more Monya Baker modification. Moreover, it is about twice as precise control over the process. fast and a hundred times more efficient than Modified RNAs can direct differentiation RESEARCH PAPERS standard techniques that use viruses to insert Warren, L. et al. Highly efficient reprogramming to as well as induce pluripotency. Induced pluri- pluripotency and directed differentiation of human genes into cells. Researchers at the Harvard potent stem cells dosed with RNA encod- cells with synthetic modified mRNA. Cell Stem Cell 7, Stem Cell Institute plan to start using the ing MYOD, an important factor for muscle 618–630 (2010). Nature America, Inc. All rights reserved. All rights Inc. America, Nature 1 © 201 18 | VOL.8 NO.1 | JANUARY 2011 | NATURE METHODS.