RNA INTERFERENCES THERAPEUTICS: A NEW APPROACH TO THE TREATMENT OF OCULAR DISEASES TERAPIAS BASADAS EN LA TECNOLOGÍA DE ARN DE INTERFERENCIA: UNA NUEVA CLASE DE FÁRMACOS PARA EL TRATAMIENTO DE PATOLOGÍAS OCULARES

EDITORIAL The RNA interference (RNAi) phenomenon was first observed in 1990 in plants. In order to obtain petunias more intense in color, extra copies were added to those plants whose gene codifies such color. To the surprise of researchers, the resulting transgenic petunias were bicolored and some were almost completely white. This suggested that not only transgenes had been repressed but also the plants native genes. This phenomenon was known as post-transcriptional gene silencing (PTGS). Later on, in 1998, Fire and his colleagues described for the first time the phenomenon of genetic inter- ference or RNAi. They noticed how the double strand DNA injection (dsDNA) within the Caenor- habditis elegans nemotode resulted in the specific silencing of the gene of a sequence complementary to the one introduced (1). The action mechanism at the molecular level was described some time later in embryo extracts from the Drosophila melanogas- ter (2). These revealed that long fragments belon- ging to dsDNA could be divided into small portions of 22 nucleotides and how the introduction of frag- ments consisting of 21 or 22 chemically synthesi- zed nucleotides facilitated the degradation of the homologous RNA. Today, the phenomenon of inter- ference in the genetic expression mediated by small RNA endogenous interferents or siRNA has been acknowledged as a biological strategy taking place in most eucariots. Today, there is a large number of biochemical and genetic evidence which have pro- vided for the discovery of the action mechanism behind the RNAi and how the RNA messenger (RNAm) target degradation occurs (fig. 1). The introduction of the double strand RNA (dsRNA) in a cell or body results in a complex cascade which results in the degradation of RNAm. The process, located in the cytoplasm, begins when the Dicer protein captures the long double strand RNAs and divides them, resulting in a 21-25 nt siRNA (short interferent RNA). The siRNA, whether endogenous or artificially introduced in cells, is incorporated into a multiprotein complex known as RISC (RNA- inducing silencing complex). During this union, double strand siRNAs are unpaired and the antisen- se strand which remains attached will guide this complex in the search for the homologous sequen- ce of the RNAm target. Once it has found the com- plementary sequence, it pairs up with the siRNA and causes the endonucleotidic rupture by means of the Dicer protein, which degrades the transcript of the particular gene. It is worth noting the fact that one of the key factors intervening in the maintenan- ce and efficiency of interference is the ability of the