DNA chips and RNA interference

Finding targets – with the help of modern genome research

The first step in the research and development process is to identify what is known as a target: a protein that plays an active role in the disease process. The idea is that the drug will later inhibit or stimulate the activity of this protein and thus stop the pathological process. Findings from modern genome research are helping researchers in their search for potential target proteins.

Proteins control the processes in the body – both healthy and pathological processes. Instructions on how to build these proteins can be found in their DNA: all proteins are encoded by certain gene segments, some longer, some shorter. To make a protein, body cells first copy the corresponding segment of DNA. This copy – the messenger RNA (mRNA) – is subsequently translated into a protein. Each mRNA molecule thus corresponds to a specific protein. Analyzing the messenger RNA in the cell can thus yield information on the proteins formed – and thus on the processes in the body targeted by the cell.

Protein production can be measured – with DNA chips

In their search for a suitable target protein, the researchers analyze the amounts of messenger RNA in healthy cells and compare the result with levels in diseased, e.g. cancer cells. To do this, the messenger RNA is marked with fluorescent dyes and brought together with a DNA chip, where it binds to its counterpart gene. This produces a measurable light signal, making it possible to measure exactly which sections of DNA on the chip are targeted how frequently by messenger RNA molecules, i.e. which proteins the cell makes. If diseased cells are seen to contain messenger RNA molecules that are not found in healthy cells, or in different amounts, it seems likely that the corresponding proteins might be involved in the disease process. This makes them interesting target candidates.

Transmitter for 'jamming' proteins: RNA interference

The researchers then use cell cultures to verify the target candidate's supposed role in the disease process. Molecules are introduced into the cell that breaks down its messenger RNA structure, thus specifically suppressing the production of the protein. In line with their jamming function, these molecules are called small interfering RNA (siRNA). This method, also known as RNA interference (RNAi), can also be used to block the formation of any target protein. If the targeted 'elimination' of a single protein leads to a change in the pathological process, it proves that this protein is actively involved in the disease process and a possible target for a drug.

Systematic search for targets using robot technology

Today, every gene in a cell can be systematically targeted and the formation of the corresponding protein 'switched off' with the help of robotic technologies. In this way possible target proteins can be analyzed by RNA interference in just a few weeks. The automated process also enables observations to be made indicating hitherto unknown target candidates.

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