Nature Journal Club

Robert Langer

Massachusetts Institute of Technology, USA

A bioengineer sees a future for safe gene-silencing therapies.

The possibility of treating genetic disorders by modifying gene expression has been an attractive yet elusive goal for decades. Problems with the safety and efficacy of various types of gene therapy have held back progress. In particular, there have been some high-profile failures, including a number of deaths during clinical trials.

But seminal studies reported by Andrew Fire and Craig Mello in 1998 led to a potentially new class of therapeutic agent. These researchers, who went on to share a Nobel prize for their work, found that small pieces of RNA, dubbed siRNAs, can silence genes.

Although switching off genes may have fewer complications than adding new ones, the safe and effective delivery of genetic agents remains a critical challenge. I was therefore pleased to see a recent paper reporting tests of an siRNA-delivery system in monkeys (J. Heidel et al. Proc. Natl Acad. Sci. USA 104, 5715–5721; 2007), suggesting that safe, repeated systemic administration of siRNAs is possible.

Mark Davis of the California Institute of Technology in Pasadena and his colleagues created nanoparticles composed of siRNAs and a novel polymer based on the sugar cyclodextrin. These particles were injected into the monkeys and their health was monitored. The monkeys tolerated multiple doses of siRNA of increasing amounts.

This paper was of interest to me not only because my group works on lipid formations that might serve as delivery systems for siRNA or other genetic agents, but also because I was pleased to see a former student doing well. Jeremy, the first author, once worked in my lab as an undergraduate.

Studies such as this one are bringing back to the field the excitement that surrounded gene therapies in the 1980s.

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