Grant: Operating Grant - PA: HIV/AIDS Research Initiative - Biomedical/Clinical Stream

Nature has developed mechanisms to protect living organisms against external intruders such as viruses, or internal dysfunction such as that leading to cancer. This security mechanism is shutting down genes and is known as gene silencing. Gene silencing is at the heart of cell development and specialization. Gene silencing is nowadays widely used to study human and model organisms' genetics and development, and to create transgenic plants that can resist to viruses. Accumulating evidence points to the fact that cancer results from the deregulations of multiple genes simultaneously. Occasionally, the cell is unable to activate properly its defense mechanisms, and this can result in cancer progression. Similarly, when a virus such as HIV invades a cell, it uses the cell's own genes to establish itself and reproduce. From our current understanding of how the gene silencing machinery works, we can engineer transgenic plants, but also fight against diseases such as cancer and AIDS. Gene silencing is based on a class of ribonucleic acids (RNA) called microRNAs. Recent developments in biochemistry techniques allow us to create artificial microRNAs (amiRNAs) and to introduce them in the cell. Drs. Major and Ferbeyre are developing amiRNAs that can silence a set of predetermined genes simultaneously. Here, they want to improve this approach by demonstrating that if they know in advance the genes that must be shut down, then they can develop a therapy based on the engineering of a single amiRNA against these genes. They are joining their efforts and respective expertise in RNA engineering and cancer biochemistry to target simultaneously the key genes involved in human prostate cancer and essential HIV components.