Small interfering RNA molecules (commonly known by the acronym siRNA small interfering RNA) represent one of the most revolutionary innovations in molecular biology and precision medicine. Their discovery, by scientists Andrew Fire and Craig Mello, was a milestone in biological research and was awarded the Nobel Prize in Physiology or Medicine in 2006.
History of the discovery of siRNAs
In 1998, Andrew Fire of Stanford University and Craig Mello of the University of Massachusetts, both biochemists, announced the discovery of a completely new way of regulating gene expression.
They found that small RNA molecules could effectively silence specific genes. Their research, which was based on experiments in the nematode Caenorhabditis elegans, showed that siRNAs were able to trigger a process known as RNA interference, allowing genes to be selectively switched off. This finding, known as “double-stranded RNA interference”, revolutionised the understanding of gene regulation and opened new doors for the development of gene therapies.
Through their work, Fire and Mello helped discover that RNA interference was a natural mechanism present in the cells of many organisms, using small RNA molecules, called siRNAs, to silence specific genes by binding to the corresponding messenger RNAs (mRNAs) and preventing them from being translated into proteins.
This discovery had a significant impact on research in molecular biology and genetics, providing a powerful tool for the regulation of gene expression and the study of specific gene functions.
The 2006 Nobel Prize
Fire and Mello’s work did not go unnoticed by the scientific community. In 2006, they were awarded the Nobel Prize in Physiology or Medicine in recognition of their discovery. The Nobel Committee noted that their research had the potential to transform medicine and gene therapy, as siRNAs could be used to silence genes responsible for both diseases and genetic disorders.
Applications in precision medicine
siRNAs have proven to be a valuable tool in precision medicine, which focuses on personalised treatments tailored to the needs of each patient. siRNAs allow for the targeted regulation of genes, which is essential in the treatment of rare diseases. These diseases, which affect a small number of people worldwide, often lack effective treatment options due to a lack of therapeutic focus.
siRNAs can target defective genes responsible for rare diseases and selectively switch them off, providing a highly precise therapeutic approach. This means that patients with rare diseases can receive personalised treatments designed to correct the underlying causes of their conditions, rather than simply alleviating symptoms.
The future of siRNAs in medicine
The discovery of siRNAs by Andrew Fire and Craig Mello has paved the way for a new era in precision medicine. As research progresses, we are likely to see an increase in the development of siRNA-based therapies for a variety of rare and genetic diseases. This offers renewed hope for patients who previously had no viable treatment options.
In summary, the discovery of siRNA molecules by Fire and Mello has had a lasting impact on contemporary medicine, enabling more precise and personalised treatments for a wide range of diseases, especially rare ones. The silent revolution of siRNAs continues to provide new opportunities in the field of gene therapy and reminds us of the power of scientific research to transform lives.
The OLIGOFASTX Consortium: transforming hope into reality
Within the OLIGOFASTX consortium, Sylentis is at the forefront of applying these RNA molecules to develop innovative treatments in ophthalmology. Its most advanced drug, tivanisiran, is already in Phase 3 clinical trials and has another in Phase 2. In the OLIGOFASTX project, it is developing new molecules to combat rare diseases that affect vision, such as Retinitis Pigmentosa, Leber Congenital Amaurosis and Älstrom’s Syndrome.
These diseases, due to their genetic nature, require highly specific and personalised therapeutic approaches. siRNAs, with their ability to selectively silence defective genes, have become a critical piece in the arsenal of tools used by Sylentis and the OLIGOFASTX consortium to combat these debilitating diseases, providing real hope for patients who previously lacked effective treatment options.