Australian scientists have recently made a groundbreaking discovery that could revolutionize the field of RNA-based therapies. This discovery might pave the way for more effective and longer-lasting RNA-based medicines, offering a broader range of potential applications.
In a recent publication in the prestigious journal Nature, researchers from the Peter MacCallum Cancer Centre, including Vi Wickramasinghe and Linh Ngo, along with collaborator Greg Goodall from the University of South Australia and SA Pathology's Centre for Cancer Biology, have unveiled a new pathway. This pathway could potentially address a significant limitation of current RNA-based therapies.
Presently, these innovative therapies rely on mRNA, a type of genetic material that can be injected into the body to produce therapeutic effects or vaccines. However, one major drawback is that mRNA tends to degrade rapidly once it enters the body.
Dr. Wickramasinghe, the senior author of the paper, explains that the linear structure of mRNA is what makes it unstable inside the body. This instability has hindered the widespread application of RNA-based therapies for diseases such as cancer.
To overcome this challenge, there has been growing interest in another form of RNA called circular or circRNA. CircRNA has a closed-loop structure, which makes it more durable. However, the precise mechanisms by which circRNA functions within cells have remained elusive until now.
The researchers have now uncovered how circRNAs, produced in the nucleus of cells, are transported out of the nucleus to carry out their functions in the cell's body, known as the cytoplasm. Understanding this transport pathway is a significant step toward harnessing circRNA for therapeutic purposes, similar to mRNA.
Professor Goodall highlights that the transport mechanism of circRNA resembles how some proteins are transported out of the nucleus, rather than the mechanisms used for other types of RNA. This finding further supports the notion that circRNAs play crucial roles within cells.
With the molecular mechanism elucidated, possibilities for manipulating it for beneficial outcomes such as disease therapies are now within reach.
This research represents a collaboration between the Peter MacCallum Cancer Centre, the Centre for Cancer Biology at SA Pathology, and the University of South Australia. Funding for the study was provided by various organizations, including the NHMRC, veski, the Victorian Cancer Agency, and the National Breast Cancer Foundation (NBCF).
Dr. Wickramasinghe recalls that when this work commenced in 2017, it was purely exploratory research. Little did they know that years later, the world would witness the advent of the first mRNA vaccines during the COVID-19 pandemic.