How small RNA molecules impact biomedical research
The discovery of small RNA molecules and their relevance for gene regulation has dramatically changed our understanding of many essential cellular processes — and provides the opportunity to develop new ways for treating various diseases. By selectively inhibiting gene expression and thereby “silencing” genes involved in pathogenesis, the RNA molecules constitute a unique tool to treat cancer, neurological disorders or viral infections and other human diseases.
At theXX International Congress ofGenetics, held in Berlin from July 12-17, 2008, renowned experts willpresent the results of their latest research in RNA biology and discusspotential applications.
The process by which small RNA molecules inhibit gene expression iscalled RNA interference or „gene silencing“. Andrew Fire and Craig Mellowere awarded the Nobel Prize in Physiology or Medicine in 2006 for thediscovery of RNA interference. Only eight years before, the US-Scientists had shown that by injecting double-stranded (ds) RNA molecules into theroundworm Caenorhabditis elegans the expression of homologous genes isinhibited.
Another set of small RNA molecules, named microRNAs, was discovered in2001.These are of endogenous origin and likewise regulate geneexpression by base-pairing to and degrading mRNA. The therapeuticpotential of RNA interference was immediately recognized once it wasshown that it also works in mammalian cells. Theoretically, small RNAscan be constructed and directed against any known gene sequence.Aberrant genes can thereby be silenced and pathogenic processes eliminated.
“The tremendous significance of microRNAs for gene regulation anddevelopmental processes was not predictable five years ago, when thelast International Congress of Genetics took place in Melbourne”, saysProf. Dr. Alfred Nordheim, Secretary General of theXX InternationalCongress of Geneticsin Berlin. “Today, small RNAs are increasinglydeveloping into a therapeutic tool and there is reasonable hope that thiswill be successful in the near future”, Nordheim, head of the Departmentof Molecular Biology at Tübingen University, assumes.
Promising results have already been reported in several animal modelsand also in clinical trials. In patients with macular degeneration forexample, the debilitating growth of blood vessels was stopped with smallRNA molecules against the growth promoting factor VEGF. Before thewidespread implementation of RNA therapies, several obstacles have tobe overcome. For example, scientists have to improve transportefficiency into the cells, find ways to prevent the molecules from beingdegraded in the cytoplasm and enhance their specificity for the targetRNA.
Apart from RNA genetics, modern genetic research is already contributinga lot to fight human diseases. In recent years, improved sequencingtechniques made it possible to rapidly diagnose infectious bacteria orother pathogens. Bacterial cultures of patient specimens, which oftentake days to grow in the laboratory, thus become redundant, andeffective therapies can be implemented sooner. “There is hardly adisease without a genetic component”, Prof. Alfred Nordheim explains:“Not only pathogens, but also food, lifestyle or radiation can make us sick by influencing and changing our genetic information or its expression. Weare now beginning to understand the functioning of a cell on themolecular level.”