杏吧原创

A way of packaging messenger RNA inside a human protein might make it much easier to deliver mRNA to cells in specific organs. This would allow mRNA聽to be used to treat a wider range of conditions, from inherited diseases to autoimmune disorders to cancers.

Using a human protein shouldn鈥檛 provoke an immune response, meaning people can be given repeated doses of the same treatment.

鈥淭his protein is found in the human bloodstream,鈥� says an investigator at the Howard Hughes Medical Institute who is based in Massachusetts. 鈥淲e feel it is not immunogenic,鈥� he says, meaning it wouldn鈥檛 trigger the body to reject it.

The success of the leading coronavirus vaccines has demonstrated the great potential of the mRNA approach. Instead of making proteins in factories, which is difficult and expensive, this technique is based on delivering genes instead and letting the body do the hard work of making proteins. The mRNAs are copies of genes that don鈥檛 get integrated into cells鈥� genomes and break down after a few days, so their effect is temporary.

But delivering genes to cells is tricky. One approach is to package them inside the shell of a virus. The trouble is that the immune system targets the viral shell, so individuals can鈥檛 be dosed repeatedly.

In the Pfizer/BioNTech and Moderna covid-19 vaccines, mRNA is instead encapsulated in oily droplets called lipid nanoparticles, injected directly into the muscles in your arm. These don鈥檛 provoke an immune reaction, but if lipid nanoparticles are injected into the bloodstream, they get mopped up by the liver within half an hour. This is ideal for, say, treating protein deficiencies in the liver, but not for treating brain or heart disorders.

Zhang and his colleagues鈥� method could combine the advantages of both approaches. They have shown that mRNAs can be packaged inside a human protein called PEG10 that forms virus-like particles. PEG10 originally derives from a kind of genetic parasite called a retrotransposon, but the protein was co-opted by mammals early in their evolution and now plays a key role in the development of the placenta.

By adding various targeting proteins to the outside of the virus-like particles, mRNAs can be delivered to any desired cell type.

Among other experiments, the team has shown that the method can deliver mRNAs coding for the CRISPR gene-editing machinery to human cells growing in culture. The method will still require a lot more work to improve it, says Zhang, and confirmation that there is no immune response will be crucial.

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