The role of RNA in the response to cellular stress

点击翻译按钮获取中文摘要

Recently, a new gene delivery system has been developed, to specifically provide diseased cells with a particular protein to correct cell function. This method using messenger RNA molecules as a delivery vehicle. By changing the RNA molecules different proteins can be encoded on these RNA molecules and different human disease can be treated. However, our lack of understanding of these molecules has resulted in safety issue, which need to be resolved before they can be used to treat a large range of human diseases. Our laboratory has been investigating how RNAs are regulated and we have discovered that two particular RNA binding proteins associate with translationally repressed mRNAs. Using methods developed in our laboratory we can now identify RNA repression mechanisms operating in different tissues and thus tailor these RNA molecules for specific delivery to different tissue types, reducing toxic side effects. We will determine the applicability of this approach to identify the repertoire of repressive mechanisms operating within a cell, in order to engineer therapeutic-mRNAs for restricted on-target expression in particular tissues/cell types and disease states. This will facilitate the development of the next generation of mRNA-based therapeutics which will be specifically designed to minimise potential off-target adverse effects.