Genetics and stem cells

New clues to fighting genetic disease

“Scientists have hit on a genetic trick that opens up fresh avenues for the treatment of devastating diseases, such as cystic fibrosis, muscular dystrophy and certain forms of cancer,” reported The Guardian.

The news comes after laboratory researchers found a way to get cells to “ignore” a certain type of genetic mutation. The mutation in question – called a premature stop or “nonsense” mutation - leads cells to prematurely halt the construction of a protein, instead creating a shortened protein that may not work correctly or may not work at all. The researchers showed that applying a certain chemical modification allowed yeast cells to bypass a nonsense mutation and produce a full-length protein. The researchers reported that about a third of human genetic diseases are caused by this type of mutation.

Although this well-performed study had exciting results, we cannot be sure yet whether a similar approach would work on humans. Much more research is needed and, even if the method could be applied in humans, developing it into a safe, proven application for the treatment of human genetic diseases will take some time.

Where did the story come from?

The study was carried out by researchers from the University of Rochester, USA. Sources of funding for the research were not reported. The study was published in the peer-reviewed scientific journal Nature.

This story was covered in The Daily Telegraph, Daily Mail and The Guardian. All three papers implied that the results of this experimental study, conducted in animal cell extracts and yeast, could apply to the treatment of human genetic diseases. The Telegraph and the Mail did go on to state that the experiments were performed in yeast. Appropriately, the Mail included a quote from Dr Philippa Brice that highlights the early stage of this research: “This discovery is a tremendously exciting development for genetics, but there are major barriers that will need to be overcome before it could be used to treat genetic diseases.”

What kind of research was this?

This laboratory research investigated whether the production of proteins in cells could be altered in a controlled way.

The DNA within genes contains the genetic instructions needed for making various different proteins. The DNA sends these instructions to the cells’ protein-making machinery using molecules called messenger RNA (mRNA). The mRNA effectively tells a cell how to fit together specific sequences of amino acids to form a protein. Certain genetic sequences also instruct the cell that a protein is complete, so that it will stop production. If mutations cause this “stop signal” to occur earlier within the mRNA, it will prematurely halt the protein-making machinery, creating a shortened protein that cannot perform its normal function. Approximately 33% of genetic diseases are reportedly caused by an error in the DNA sequence that causes the mRNA to contain a premature stop signal.

This research aimed to determine whether the researchers could modify a premature stop signal in the mRNA so that the protein-making machinery could bypass it and produce a full-length protein.

This well-performed research provides novel findings. However, much more research will be needed to determine whether these findings could help treat human genetic diseases.

What did the research involve?

The researchers first carried out experiments in extracts from rabbit cells, and then in live yeast cells. They looked at whether a specific chemical modification might allow the cell to ignore stop signals in mRNA, allowing a full-length protein to be produced.

In their first set of experiments in rabbit cell extracts, they compared protein production using mRNA with a premature stop, mRNA with a premature stop that was chemically modified, and mRNA without a premature stop.

Next, the researchers moved on to live yeast cells. The yeast used in this experiment would normally die if exposed to a particular environmental exposure but the researchers genetically engineered the cells to carry instructions for making a protein which would allow them to survive when exposed. However, the mRNA for this protein also contained a premature stop that would prevent the full protein from being produced. They also genetically modified the cells to produce a naturally occurring type of molecule that could chemically modify the premature stop in the mRNA. If the yeast cells survived, it would indicate that this second modification successfully allowed the yeast cells to bypass the stop signal and continue protein production.

The researchers then determined which amino acid “building block” was being incorporated into the protein in the place of the stop signal.

What were the basic results?

In the first phase of their study in rabbit cells, the researchers found that protein production was almost the same when cells used the mRNA with the chemically modified premature stop and the mRNA without a premature stop. The non-modified premature stop prevented the cell extract from producing the full protein.

Once this had been shown, the researchers went on to test whether the modification could work in live yeast cells. They found that the genetically engineered cells could chemically modify the premature stop, and that this allowed a full-length protein to be produced. This meant the yeast cells could grow in an environment where they would normally die.

How did the researchers interpret the results?

The researchers concluded that this targeted modification of stop signals is a “novel approach” for promoting stop signal suppression in live cells. They say that this finding “is of significant clinical interest” as premature stop mutations are estimated to account for about a third of genetic diseases.


This exciting, novel finding allows full-length proteins to be produced from mRNA with premature stop signals. However, it was performed in yeast, and any translation into a clinical setting for treating genetic diseases is a long way off. There are several points to consider:

  • Not all genetic diseases are caused by stop mutations. Therefore, even if this approach could be used in humans, it would not be applicable in all human genetic diseases.
  • This study was performed in yeast, which is used in research as it is easy to manipulate. How the signal to modify premature stop signals could be delivered to human cells would require further research.
  • Proteins are made up of amino acid “building blocks”. The mechanism used in this study works by incorporating certain amino acids into the protein instead of prematurely stopping their production. These amino acids may not be the same ones that would be included in the normal form of the protein, and therefore it might not work in its normal way.
  • It is not clear how localised this type of modification would be. Research would need to ensure that the technique would not affect the production of other proteins in the cell.

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