Impact of Nucleic Acid Chemistry on Gene Function Analysis

Organisers:

Joachim W. Engels, Institut für Organische Chemie, Goethe Universität Frankfurt am Main
Hans Prydz, Biotechnology Centre of Oslo
Jutta Reinhard-Rupp, Functional Genomics, Aventis, Frankfurt am Main
Kathrin Heermeier, Functional Genomics, Aventis, Frankfurt am Main

e-mail: kathrin.heermeier@aventis.com

Background:

In 1977 Paterson et al. noted for the first time that gene expression could be modified using exogenous nucleic acids. Ever since, researchers have used antisense nucleic acids to manipulate gene expression and thereby identify gene functions in the context of a cell or organism. Several different techniques have been developed and improved over the years. However, after decades of research and technology development, the field of antisense based techniques is still moving fast. RNA interference (RNAi) is just the latest example of a number of novel developments during the past years and months. Today, considering the large number of genes awaiting functional analysis, there is an increased need for broadly applicable technologies allowing for fast and inexpensive yet specific determination of gene function. Technologies based on antisense nucleic acids, such as antisense oligonucleotides, ribozymes, aptamers, and RNAi fulfil this need.

The aim of this workshop is to facilitate communication and foster collaboration between groups of researchers using techniques that are different but highly related. Experimental approaches differ in the chemical nature of the reagents ranging from short oligonucleotides, single or double stranded, synthesised with specific chemical modifications, to larger RNAs generated from DNA constructs within the cell like ribozymes. Another important difference between methods is the cellular mechanisms of action. However, they all interfere with gene expression on the level of mRNA through sequence specific binding. The common goal is to manipulate gene expression and to study gene function. There is a number of common problems including site selection, delivery of the reagents to the correct cellular compartment, stability, specificity, toxicity, etc.

A session will be dedicated to accessibility of RNA. This is a common problem in all techniques using antisense. The prediction of secondary structures has greatly improved, however, computer models can not predict folding of RNA within the cell in the presence of known and unknown proteins binding to nucleic acids. Different strategies have been used to overcome this problem: covering the whole sequence with oligonucleotides and analysing them empirically, using sites within the gene that have a high likelihood of being accessible such as the start of the coding region, using computer modelling in spite of its limitations, and a combination of all.

Another session will cover antisense oligonucleotides and ribozymes, techniques that have been used successfully for target validation for many years. One can expect to hear more presentations with a focus on biological questions and less technology development even though these techniques, in addition to generating functional data, are still evolving too.

RNAi is the latest approach to use sequence specific binding of antisense nucleic acids to modify gene expression. Double stranded RNA is used to inhibit mRNA. Progress has been made very rapidly during the last 3½ years, first using the technique in model organisms like Caenorhabditis elegans. Its use in cultured cells seemed to be impossible in the beginning, due to severe side effects on the cell metabolism. Very recently researchers have succeeded in adapting the technique to cell culture. Since the mechanism of action within the cell is still unclear, RNAi promises to be a particularly exciting topic at the workshop.

Alternative approaches will be the focus of the fourth session. Aptamers, PNA, LNA, and other methods offer solutions for very specific problems. There will be room for new ideas and unconventional approaches that might contribute to the field and might profit from critical review and discussion.

Venue: The workshop will be held at St. Goar (Schlosshotel Rheinfels), Germany

Dates: Thursday 4th - Saturday 6th April, 2002

Atendance: The workshop is limited to a maximum of 50 places including invited speakers.

Programme:

List of speakers:

Registration:

Closed

Please note that available funding is not sufficient to cover the costs for travel and accommodation for all participants. Please wait to be contacted by the meeting organiser who will supply you with further details should you be selected to attend.

For further information, please contact Kathrin Heermeier (local organiser) or Annette Martin (programme administrator)