Over the last few years, clinical pharmacology has undergone important changes due to the incorporation of new advances in molecular biology for drug discovery processes.
Cell signalling plays a critical role in cellular functions. It controls both normal cellular growth and the appearance of alterations related to certain pathologies. There are a large number of pathologies which appear as a result of anomalous activity in defined proteins. Treatment of these pathologies can be carried out by suppressing such activities.
Recently, a new technology called RNA interference or RNAi has been developed. RNAi technology consists of a specific gene silencing thanks to small molecules of double stranded RNA. This technology is a powerful tool which has been intensively investigated with therapeutic purposes due to two facts: First, all cells contain the biological machinery for RNAi processes and, second, genes are potential targets. RNAi technology presents advantages in comparison to other therapies, including a rational design based on knowledge of the therapeutic target, high specificity and limited side effects.
In simple terms, an individual's genetic information is written in his/her DNA and is organised
into genes. In the cell nucleus, the genes transcribe the genetic information contained in the
DNA into messenger RNA (mRNA). The mRNA abandons the nucleus and binds to the cell's ribosome, which translates the mRNA sequence into the corresponding protein or enzyme. The
translation and protein synthesis can be blocked by acting on the mRNA; that is what RNAi does.
RNA interference is a mechanism for post-transcriptional silencing of specific genes: small RNA
molecules that are complementary to the mRNA cause its degradation and prevent it from being
translated into proteins.
Gene silencing using RNA interference is induced by small two-chain RNA molecules comprising
21 to 27 nucleotides, which are called siRNA (small interfering RNA). The siRNA undergo processing
in the cell in which the two-chain RNA is split into a "guide strand" and an "anti-guide strand".
The anti-guide strand binds to the specific mRNA molecule due to base-pair complementarity,
and the resulting complex is recognised and degraded by the cellular mechanisms. Each siRNA
is highly specific for degrading a target sequence of mRNA nucleotides. This gene interference
phenomenon occurs naturally in the organism and it is involved in the mechanisms of development
and in the defence against viruses.
However, siRNA can also be introduced artificially into the organism to silence a specific gene. Any gene whose sequence is known can be targeted by a specifically-designed siRNA molecule with the complementary sequence to that gene. Therefore, siRNA is an invaluable tool for examining the function of genes, validating therapeutical targets, studying drug action mechanisms, and treating diseases of genetic origin.
SYLENTIS applies RNAi technology with the aim of discovering new molecules with therapeutic activities in several diseases. The technology is applied using two methods: small interference RNA ( siRNA ) and small hairpin RNA ( shRNA ). These molecules permit us to silence the specific messenger RNA (mRNA), which is responsible for the synthesis of pathogenic proteins in the cell, inhibiting their effects.
SYLENTIS has developed the SIRFINDER Technology. This technology determines siRNA with a potential for pharmacological applications, by means of an optimized search, including bioinformatic tools. This technology reduces research times and maximizes results. A large number of molecules have shown activity against several therapeutic targets.