Thermo Fisher Scientific - A new era for RNAi

For five years the potential of RNA-interference technology to improve the drug discovery and development process has been a hot topic. Turning the principle into a practical technology platform may not have been simple, but recent studies have shown that the hype about RNAi may be justified.

The pharmaceutical industry has been closely watching the development of RNA-interference (RNAi) technology in recent years, recognising that this mechanism of gene regulation could have a significant impact on the efficacy of existing medications and the formulation of new drugs.

RNAi uses double-stranded RNA to silence a gene by eliminating its corresponding messenger RNA (mRNA), with small interfering RNA (siRNA) affecting the gene's expression. The principle has been accepted, but only now is the research catching up with the technology's spiralling potential.

In April the industry saw the first demonstration of the impact of RNAi technology on drug discovery and development. Dr Michael White of the University of Texas Southwestern Medical Centre in Dallas used technology and reagents from Dharmacon - now the RNA technologies team at Thermo Fisher Scientific - to identify 87 genes that appear to affect the susceptibility of human cancer cells to certain chemotherapy drug treatments. He found, for example, that when certain genes were silenced, the chemotherapy drug paclitaxel (Taxol) became dramatically more effective in destroying the cancer cells.

"The study impacts on big pharma's perspective on how RNAi can make drug discovery and development more effective," says Anastasia Khvorova, Thermo Fisher's chief scientific officer of RNA Technologies. "It was the first well-done, whole human genome screening to be carried out using RNAi. It took a lot of technological innovation to get to this point."

Practical technology

There have been many challenges to delivering RNAi in a practical, commercial form. Specificity was a key concern. But the ON-Target range from Thermo Fisher has helped to ensure that only the targeted genes are knocked down, and with minimum genome cell damage. High-throughput technology to handle the scale of complex genome screening has also emerged. The remaining hurdle is delivery - using RNAi in vivo and in vitro. Thermo Fisher promises a breakthrough in this area, perhaps within the year.

Solving this final problem would result in the creation of a technology that is easy to use and highly scalable, and not only put it within the grasp of elite scientists but also open it up for more widespread use in drug development.

From theory to reality

The RNAi Global Initiative, of which White is a founding member, was conceived by the team now at Thermo Fisher, and has helped accelerate the development of the technology.

"It brings together talented thought leaders from the world's leading academic institutions, and it has facilitated the technological development that has enabled people to look at reverse functional genomics as a regular part of the drug discovery and development process," believes Khvorova.

"Two years ago, most pharma companies were waiting to see if this was just another fancy technology with an unclear impact, but we have shown that it supports a value-added process that helps people to better understand the functionally of a drug. It can help reduce the toxicity and increase the potency of certain drugs," she says.

Thermo Fisher's long-term commitment to RNAi development has led it to launch high-throughput screening and analysis services through its RNAi Discovery and Therapeutic Services laboratory.

Tapping into the industry's growing appetite for outsourcing, the service offering leverages the company's technology, reagents and expertise to offer the scale of infrastructure required to screen the 22,000 genes in the human genome in a cost-efficient and timely way.

"People are convinced of the value of RNAi as a functional genomic tool, and we also believe that siRNA molecules might have their own therapeutic applications," says Khvorova.

The industry should expect the pace of RNAi development to step up a gear in the next five years.

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