Invention: Gene-silencing technique to treat diseases
Thomas Tuschl’s groundbreaking method of “switching off“ human genes has become a vital tool in developing new ways of diagnosing and treating conditions from haemophilia to high cholesterol. The biochemist succeeded in adapting a gene-silencing technique known as RNA interference (RNAi) for use in human cells.
The proteins built by our cells are necessary for our biological functions. However, when a gene gives instructions that differ from the typical blueprint, the incorrectly built proteins can cause a variety of diseases and conditions. Halting the activation of disease-causing genes can help prevent certain diseases.
Tuschl’s research exploited the specific function and behaviour of ribonucleic acids (RNA), which regulate the amount of proteins created in a cell. His breakthrough was introducing double-stranded RNA of a very specific length into a cell – large enough to induce RNAi and thus silence the target gene, but small enough not to trigger the cell’s self-defence system and cause side effects. Tuschl’s invention lays the foundation for many promising therapies and has greatly advanced our understanding of human genetics.
Today, RNAi applications are fundamental to blue sky research in the field of genetics, and part of the standard tool-kit of laboratories worldwide. Meanwhile, diagnostic and therapeutic innovations are in development by Alnylam and other biotech companies. Early laboratory successes in various diseases have yielded encouraging results. Millions of people stand to benefit from RNAi in the future.
US company Alnylam, which Tuschl co-founded in 2002, has exclusively licensed the rights for his method. He still acts in a scientific advisory position for this company. RNAi biotech start-ups have garnered billion-dollar investments from different sources, including large pharmaceutical companies. Alnylam attracted pharmaceutical giant Roche, which bought a non-exclusive licence to their technology in 2007 in a deal reputedly worth US $300 million.
No RNAi-based products or therapies have been
approved so far, but many are in clinical trials, including 11 developed by
Alnylam. The global market for RNAi research reagents, therapeutics,
diagnostics, and agriculture was valued at almost US $210.2 million in 2012 and
is projected to reach US $290 million by 2018.
How it works:
Each gene contains the code for a specific protein, encoded in the DNA. DNA is transcribed into messenger RNA (mRNA), which is transported from the cell nucleus to the cytoplasm where it is decoded and manufactured into protein.
Tuschl adapted a gene-silencing technique known as RNA interference (RNAi) for use in human cells. He introduced specific double-stranded RNA from outside a cell which had just the right length (21 nucleotides) and structure (2-nt 3’ overhang) to induce RNAi and silence the protein-coding process of the targeted gene, while remaining small enough to avoid triggering the cell’s self-defence mechanism, which would cause side-effects. The method does not eliminate the gene, only its functional product – the mRNA and the protein.
Thomas Tuschl is considered to be one of the best RNA biochemists in the world. He grew up in Bavaria and studied and worked at Regensburg University, the Max Planck Institute for Experimental Medicine and Biophysical Chemistry in Göttingen, and the Massachusetts Institute of Technology (MIT). In 2003, he became professor and head of laboratory at Rockefeller University in New York. In 2005, he was named an Investigator of the Howard Hughes Medical Institute.
Did you know?
Tuschl’s method is just one example of a number of groundbreaking advances in medical biotechnology fuelling hopes of developing radically new treatments and therapies for genetic disorders. Not only does this turn biotechnology into one of the most innovative fields of the 21st century; medical or “red” biotechnology could also become a growth engine of our times.