Genes provide the instructions to synthesise the proteins in our cells. DNA contains the information to make all our proteins, RNA is the messenger that carries this information to the ribosomes, that serve as factories, were the proteins are made. Researchers can use various techniques to achieve and modify this central process in biology.

The major mutation observed in osteosarcoma affects the gene TP53. The protein P53, which is encoded by this gene, is considered the "guardian of the genome", as it facilitates the repair of mutations that otherwise will go unchecked.

TP53 loss has been identified in over 80% of osteosarcomas, it is followed by massive genome instability, leading to the further development and progression of tumours.

What are the aims of this research project?

The purpose of this investigation is to restore TP53 in osteosarcoma cells, by using a similar messenger RNA (mRNA) technology to the one recently used to develop a vaccine against the COVID-19 virus.

This approach exploits the safety of the mRNA vaccine technology, as it does not integrate into the patient's genome, and when the treatment is complete, the mRNA would be degraded. Importantly, normal cells will be unaffected, as they do not present TP53 mutations.

The idea is to introduce a small DNA fragment that codes for TP53 RNA, as well as the machinery needed to make many copies of the RNA into osteosarcoma cells. Afterwards, the changes in both TP53 gene and P53 protein expression will be evaluated, and the researches will then study if this "restoration" of function results in osteosarcoma cell death.

The cellular experiments will be followed up with an in vivo study, where the growth of osteosarcoma tumours will be monitored in mice that are inoculated and compared with those that are not.

How could this project improve treatment options for osteosarcoma patients?

This is an ambitious and innovative project, if successful, it has the potential for a very tangible benefit to osteosarcoma patients, offering a completely novel way of treating the disease. But it also has the possibility to reach beyond osteosarcoma, as other genes could be targeted, affecting other forms of primary bone cancer.

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