The first annual RNAi Europe conference and exhibition organised by Select Conferences (18th - 19th October, 2004 central London, UK) attracted over 160 delegates including representatives from large pharmas, biotech companies academia and technology providers. The delegates were able to hear high quality speakers present the latest advances in technology and understanding of RNA is, applications in drug research and discovery and their potential as a therapeutic. As well as the 21 presentations, delegates were also able to view poster presentations submitted by a variety of companies and academics, visit the exhibition and make use of the networking opportunities provided by a cocktail reception and buffet lunches.

Bettina Hadrich, from Qiagen who presented at the event and also staffed the Qiagen booth commented "We are really happy with the conference, there are a lot of attendees; I think (it is) one of the best RNAi conferences in Europe definitely, and we would be happy to attend next year" RNAi in Drug Discovery

This two day event was kicked off by Dr. Dmitry Samarsky from Invitrogen, a well known expert in this field. Dr. Samarsky presented an informative talk covering early uses and the potential problems that can be encountered when using RNAi for gene knock down, such as activation of the interferon response in Mammalian cells and off target effects. Dr. Samarsky highlighted some of the products Invitrogen have developed to combat these problems. Discussing the fundamental differences between RNAi and Antisense, Samarsky went on to emphasize the diverse applications of RNAi. Dr. William Marshall of Dharmacon gave a well received presentation entitled "Recent advances in SiRNA Technology for application in Drug Discovery, research and development". Marshall discussed the nature of off target effects and the use of biological replicas to help understand siRNA specificity. Marshall described how using siRNA pools i.e. transfecting cells with a mixture of rationally designed siRNAs (Smartpool reagents) provides potent gene silencing and also enhances specificity, due to the lower concentration of each individual duplex being used. The highlight of this session was a presentation given by Co-founder of RNAi Professor Craig Mello (Howard Hughes Medical Institute, University of Massachusetts). Mello discussed his early work in C.elegans and the use of RNAi in studying the development of cells.

Other talks in this session were:
"Genome-wide siRNA: Development of an Automated, High Throughput siRNA Design & Synthesis Platform" presented by Dr. Bettina Hadrich from Qiagen, "High Throughput Functional Chemogenomics using RNAi for Drug Discovery" presented by Dr. David Evans from TGen "Combining siRNA gene knock-down with genome- wide expression profiling: assessment of specificity and analysis of downstream changes in biological pathways" presented by Dr. Tarif Awad of Affymetrix Genomics.

Delivery and Transfection
This session chaired by Helmuth Van Es from Galapagos Genomics, covered a range of delivery methods from the use of nanoplexs to viral transfection. Dr. David Lewis from Mirus talked about non-viral in vivo methods of nucleic acid delivery, describing and showing a movie of the Hydrodynamic Tail Vein Injection of siRNAs into mice for Gene Knockdown in Multiple Organs. The protocol involves the rapid injection into the mouse's tail vein of a sufficient volume of nucleic acid solution so as to elevate the pressure within the blood vessel and enhance the vessel's permeability, thereby enabling passage of large nucleic acid molecules to target cells outside the blood vessel.

Raymond Schiffelers from Utrecht University presented research on using nanoplex-mediated delivery to inhibit Angiogenesis in vivo. The positive charge of RNAi often causes problems when trying to get the molecule through the cell membrane into the cytoplasm. Schiffelers explained the how the use of nanoplexes can shield the positive charge of the RNAi so allowing it passing through the cell membrane.

Helmuth Van Es discussed functional screening using adenoviral siRNA expression libraries. A siRNA knockdown is inserted into the expression cassette of an adapter plasmid, which contains a short region of the adenoviral genome from which a gene needed replication has been deleted. The adapter plasmid is then transfected into a packaging cell line along with a helper plasmid which contains the remaining part of the adenoviral genome except for a second gene needed for viral replication. The packaging cell expresses the two adenoviral genes missing in the plasmids. Homologous recombination between adapter and helper plasmids after transfection in the packing cells, leads to the generation adenoviruses. The resulting viruses can be used to infect human primary cells or cell lines, as well as in in vivo animal model studies.

Other presentations in this session included:
"Optimization of functional delivery for therapeutic application of siRNA" presented by Dr. Andre Lochter of atugen. "High parallel transfection of siRNA in cell microarrays presented by Dr. Xavier Gidrol of CEA.
Target Identification and Validation

David Dorris of Ambion gave a summary of the design of SiRNAs and talked about Knockdown of Survivin as an example application. Dorris discussed the optimization of transfection highlighting several parameters to be considered; also discussed was the use of Electroporation for transfection of primary cells.

Eleanor Bernard from ExpressOn presented research on the accessibility of targets on mRNA molecules and ExpressOn's technology to determine accessible sequences within nucleic acids (AcessArray) so aiding in the design of siRNA reagents.

Explaining the design of siRNA for target validation in pain research Jens Kurreck from Berlin Free University presented data on the silencing efficiency concluding that activity of siRNA is influenced by the primary sequence and target RNA structure. Kurreck also discussed the use of siRNAs to study heart defects.

Other presentations in this session were:

"RNAi for target identification and validation in drug development" presented by Oliver Steinbach from Altana. "Many commonly used siRNAs risk off target activity" presented by Dr. Torgeir Holen CMBN, University of Oslo. "Application of high throughput RNAi and over expression technology to target validation" presented by Dr. Angelika Bonin-Debs from Xantos. Therapeutic and in vivo Developments Dr. Yvette Stallwood from Lorantis gave an interesting presentation on the use of RNAis to target Notch ligands in order to modulate immune response via Notch Pathway. Lorantis has identified siRNAs which are specific to the Notch Ligand and have shown that Knockdown of Notch ligand expression reduces Notch-Notch Ligand signalling. Stallwood concluded that Antagonising Notch signalling by RNAi or by a drug could be used to enhance immune response so have potential applications in treating many diseases such as cancer.

Dr. Nassim Usman talked about Sirna Therapeutics and their progress in developing RNAi based therapeutics. Data was presented on Sirna's work on age related Macular Degeneration using VEGFR-1 as a target showing that modification by siRNA produced significant inhibition of Vascular growth. Other presentations in this session included:

"Real time Quantitation of MicroRNAs by RT-PCR presented by Dr. Caifu Chen from Applied Biosystems. Networking and the exhibition

The exhibition was very well attended by the delegates and the exhibitors were pleased with the amount of delegates visiting their booths. Andy Walker, from MRC Gene Service, commented "we have managed to get hold of some good contacts and I think we will get some leads further down the line."

The event included plenty of time of networking and walking around the exhibition. The quality of delegates was deemed to be high with most of the key companies represented. Michael Keller of IC-Vec Ltd found the event very interesting and said "It was very well organized and all the key players are here which is very good for networking and getting to know people and exchanging views and news"

Bernd Korn, from the German Resource Centre added "I have found the conference very interesting and also very entertaining and a good opportunity to meet the key people in the field."

Summary
Many speakers emphasized the problem of off target effects when using RNAis for both target validation and as potential therapies and the need to take steps to ensure a high level of specificity, Olaf Birkeland, CSO from Interagon commented "There has been a lot of discussion on off targets, which is probably becoming more and more important, but I think really the next stage will be more Micro RNA and eventually the effect of this now turning out to be important."

There is still much excitement about the potential of RNAi and this was very much reflected in the presentations and the enthusiasm of the delegates. Eleanor Bernard Operations Director and co-founder for ExpressOn Biosystems Ltd. commented

"I think RNAi is going to continue to be a very popular tool. I think it has a way to go before it can be used as a therapeutic, but I am sure that progress will be made. I think the field is moving very rapidly."

Andre Lochter from atugen commented on the future of RNAi technologies "There has been hype for quite some time and we are at a crucial point, over the next couple of years to see how robust the technology is and how it will work across the board for different companies for in vivo applications. We have to await the first clinical data, but clearly the potential in enormous."

The general feeling amongst delegates was that the potential of RNAi is vast but there is still a lot of work to be done. Join Select Conferences at the 2005 event to find out what progress has been made in this exciting area of drug discovery. The 2nd Annual RNAi Europe conference and exhibition will be held in Amsterdam 28th - 29th September 2005

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