|Subject: [Hangout - NYLXS] Rise of the RNA machines: Self-amplification in
|Rise of the RNA machines: Self-amplification in mRNA vaccine design
Rise of the RNA machines: Self-amplification in mRNA vaccine design
by Wageningen University
Schematic representation of the protein of interest expression induced
by a conventional mRNA and a replicon vaccine. Once released in the
cell, the mRNA is translated to produce the protein of interest. In
contrast to mRNA, replicon RNA encodes alongside the protein of
interest, self-amplifying genes (depicted in blue) that amplify the
replicon RNA. This intracellular amplification will subsequently result
in higher expression levels of the protein of interest. Credit: Trends
in Biotechnology (2023). DOI: 10.1016/j.tibtech.2023.05.007
The next generation of self-replicating mRNA vaccines could have fewer
side effects such as fever, headache and fatigue. This would partly
result from the application of artificial intelligence in vaccine
development. This is the prediction of Gorben Pijlman, virologist at
Wageningen University & Research (WUR), and colleagues, published in
Trends in Biotechnology.
mRNA vaccines won the race in the early approval of COVID-19 vaccines,
but they also cause side effects such as fever, headache and fatigue.
Improvements are needed to maintain their leading role in infectious
disease control. According to Pijlman, the possible solution lies in a
next generation of self-amplifying mRNA vaccines and the use of
An mRNA vaccine contains a piece of genetic information (RNA). That
information causes the body to produce a characteristic protein of the
virus: the spike protein. Parts of this protein are recognized by immune
cells in the body. This causes the immune cells to spring into action
when an actual infection occurs.
"We think that a building block needs to be added to these mRNA
vaccines," says the WUR researcher. "A copy machine that causes the
delivered RNA to replicate in the body; these so-called replicons, or
copied RNA, ensure powerful responses with few side effects after
immunization with a single, low dose. Replicon vaccines have already
been used for animals for some time, with great success. In India,
vaccines that work this way for humans are now also permitted."
The copy machine, or polymerase (protein), is currently derived from a
virus. Pijlman expects scientists to be able to make it themselves in
the future, for example with the help of artificial intelligence. "With
the implementation of artificial intelligence in protein design, we
expect it will be possible to design small, efficient polymerases based
on the structure and shape of all viral polymerases in public
databases," he explains.
But these future AI replicons may not be covered by current legislation
on genetically modified organisms (GMOs). They are not from or
associated with any particular virus family. In other words, these
advanced "RNA machines" will not be subject to GMO legislation and/or
registration procedures that could restrict or at least delay the market
authorization of replicons.
Pijlman states, "Nevertheless, it remains important to mitigate any
risks of replicons to humans, animals and the environment. Clear
legislation is needed to do this properly; in any case, technology is
moving faster than regulations can keep up."
Pijlman points out that replicons are not only deployable against
infectious diseases: "Replicons could also play a role in inducing an
immune response against cancer. In addition, they could protect against
multiple diseases or different variants of a disease. A lot is possible
in the future."
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