RNA Interference Technology in Drug Validation and Development: RNomics Approach.

Abstract

The frontiers of modern molecular biology highlight the recent discovery of RNA interference (RNAi). In 1998, Fire et al. made the startling discovery that double-stranded RNA (dsRNA) could induce a potent silencing effect on homologous genes in the nematode Caenorhabditis elegans [1]. In addition, potent and specific gene silencing could be achieved in human cells transfected with small interfering RNAs (siRNAs) of 21–23 nucleotides, a key intermediate in the RNAi pathway [2]. Interestingly, single-stranded 21-nucleotide microRNAs (miRNAs) are identical in length to siRNAs and are also involved in the RNAi pathway [3]. The discovery of RNAi, siRNAs and miRNAs has ignited a firestorm in the field of molecular cell biology. Most of the earlier inventions in this field have emerged from the Northeast academic corridor in the US. Thus, GeneExpression Systems of Waltham has identified a ‘market-niche’ in the knowledge management sector and organized its first international conference on the theme of ‘RNAi-2003-Boston’ meeting on ‘RNA Interference Technology in Drug Validation and Development’ held in Waltham City, MA, USA (May 5–6, 2003). The conference was very well attended and scientists were present from several countries including Canada, Finland, France, Germany, Japan, Singapore, South Africa, Taiwan and the Netherlands for this one-track 2-day event. There were 25 speakers invited from Harvard, the University of Massachusetts and Massachusetts Institute of Technology. Executives from RNAi reagent-developing companies, including Ambion, Benitec Australia, BDClontech, Dharmacon, Imgenex, Promega, Qiagen, Sequitur and US Genomics, presented the details of recent product lines. The meeting was well balanced by bringing together speakers from RNAi start-up and pharmaceutical companies such as Abbott, Alnylam, Anadys, SiRNA Therapeutics and Wyeth, who exploit the RNAibased technology platform for the target validation and the development of new generations of therapeutics. In his welcoming address to a packed room, the chairman of the meeting, Krishnarao Appasani, a former researcher from Harvard Medical School and PerkinElmer, said “People anticipate that the whole pipeline is going to be reduced in drug development” because RNAi will speed up target validation so much. However, he cautioned that with any new technology in the life sciences field, its effect is not always apparent [101]. He also pointed to the surge in publications related to RNAi: a PubMed search for 1998 shows that there were only 11 papers on RNAi, whereas in 2002 the number had jumped to 421 (Figure 1). In addition, there is an emerging trend in the patent applications in the field of RNAi. In 2001, there were only 2 patents filed, whereas by the end of 2002 the number had increased to 90 (Figure 2). Because of the importance of this phenomenon and the increasing curiosity, Science quoted RNAi as the ‘breakthrough of the year 2002’ [4]. As a result of the excitment surrounding this topic in science and the hype also generated in the business world [5], several start-up companies have blossomed and most of the large pharmaceutical companies have opened RNAi-based groups for target and drug validation studies [6]. The terms ‘genome’, ‘proteome’ and ‘glycome’ are now relatively common place, but another scientific buzz word that is currently spreading fast in the research community is ‘RNome’; the subject is referred to as ‘RNomics’. RNomics is a newly emerging field that categorically studies the structure, function and processes of non-coding RNAs in a cell [7,8]. The one track 2-day meeting was arranged into eight scientific sessions and concluded with a panel discussion.