Mirimus develops enhanced tools for reversible gene suppression

Published on December 17, 2013 at 1:40 AM · No Comments

Over the last decades, RNA interference (RNAi) has become an indispensable tool for functional genetic studies by harnessing the power of a cell intrinsic mechanism enabling reversible gene silencing. Indeed, gene silencing can mirror gene loss during disease progression or mimic pharmacological target inhibition even where no such drug currently exists. In both cultured cells and animals, RNAi thus promises to rapidly advance our understanding of disease and search for new therapies.However,the design of potent and specific RNAitriggers is nottrivial, limiting the practical potential of RNAi for research and clinicalsettings.

Evolution driven design

Christof Fellmann, Johannes Zuber and coworkers at Cold Spring Harbor Laboratory (CSHL), USA, came up with strategies to improve RNAi technology when both were still working there. "The molecular underpinnings of efficient gene silencing are yet to be fully understood. Potent RNAi triggers are rare and have to be identified among hundreds to thousands of possibilities for each gene. To advance current techniques, we looked at the evolutionary conservation of natural RNAi triggers to build enhanced synthetic analogues", Fellmann describes their approach. He continued to evolve this concept at Mirimus, a spin-off company from CSHL, while Zuber went on to found his own lab at the IMP, Austria.

One particularly powerful RNAi method pioneered among others by Gregory Hannon and Scott Lowe at CSHL relies on embedding synthetic short hairpin RNA (shRNA) sequences into naturally occurring microRNA backbones. The resulting RNA molecules mimic natural triggers and are processed by cell intrinsic pathways. Yet, the efficiency of current reagents designed in this manner remains limited.

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