Cell suicide by a programmed process – apoptosis – is necessary for human health. It starts long before birth, sculpting us as embryos. It is essential for the proper functioning of our immune systems and of organs that continually produce new cells, like the intestines and bone marrow. When it goes wrong, it can lead to strokes, heart attacks and cancer. Its subversion by microbes plays a crucial role in Aids and many lethal infections. Todd Rider and his colleagues at MIT’s Lincoln Laboratory may have found a way to use the enzymes that make it happen – caspases – as antiviral agents.
They’ve engineered proteins they call DRACOs (Double-stranded RNA-Activated Caspase Oligomerisers) that get into cells, bind to double-stranded RNA, and activate caspases when two or more of them stick to the same molecule. The double-stranded RNA in normal cells, unlike the RNA produced by viruses, is too short to accommodate two DRACOs. So only infected cells will be killed.
All viruses produce long double-stranded RNAs, so DRACOs should, in theory, work against all viruses. So far so good. A paper published at the end of last month by Rider and his colleagues in PLoS ONE shows that DRACOs work well in laboratory tests using cells in culture infected with many different viruses, including those that cause the common cold and dengue fever. They also work against influenza in mice.
DRACOs look very promising. Their mode of action is rational and novel. But there’s still lots of work to be done. Cells are not people and mice are not men. Serious side effects have to be ruled out. But the benefits could be enormous. Curing rabies or HIV infections may be possible – in theory. Optimism must be tempered, however. Reflect on what often happens after the introduction of a new therapeutic agent. It starts with a handful of dramatic cures. It is puffed as ‘a wonderful development and a major breakthrough’. But side effects emerge and ‘it shouldn’t be given to a dog.’ Finally, it enters the pharmacopoeia with the rubric ‘under well controlled circumstances it is beneficial in certain cases’.
The Lincoln Laboratory was founded in 1951 by the US Air Force. It currently defines itself as a ‘federally funded research and development center chartered to apply advanced technology to problems on national security’. It likes acronyms. Its first, in 1954,was SAGE, Semi-Automatic Ground Environment, a computer-driven air defence radar system. A more recent one is TCAS, the Traffic Collision Avoidance System used in civilian air traffic control. Outsiders say that its staff exude TLA, Typical Lincoln Arrogance. DRACOs have a real chance of being another justification for it.