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to stimulate beneficial immune-signalling pathways.However, excessive stimulation can backfire, for example, when the vaccine prompts the immune system to block RNA replication, thereby nullifying its benefits.It is a delicate needle to thread, says Niek Sanders, a gene-therapy researcher at Ghent University in Belgium and a scientific founder of Ziphius Vaccines, a company in Merelbeke, Belgium, that develops saRNA-based medicines."You have to find the optimal dose of the self-amplifying RNA in combination with the right delivery system."The biotech industry has tried for decades to get the balance right.From 2003 to 2010, for instance, a company called AlphaVax, based in Research Triangle Park, North Carolina, conducted trials of saRNA vaccine candidates for a range of infectious diseases and cancers.AlphaVax ultimately wound down for "business reasons" after failing to secure further investment, says the firm's co-founder Jonathan Smith, who continues to develop saRNA vaccines as the chief scientific officer of VLP Therapeutics in Gaithersburg, Maryland.