The highly-studied, human p53 gene is known to play a key role in cellular stress response mechanisms by converting a variety of different stimuli into cell growth arrest or apoptosis (cell death). Such stimuli may include DNA damaging conditions, like gamma-irradiation, deregulation of transcription or replication, and oncogene transformation.
Most anti-cancer therapies meant to target cancerous cells also damage or kill normal cells containing native p53, causing severe side effects. Specifically, radiation therapy and chemotherapy may cause severe damage to the lymphoid and hematopoietic system and intestinal epithelial tissue, which may limit the effectiveness of these therapies and may cause hair loss. Since such side effects are to a great extent determined by p53-mediated death of normal cells, the temporary suppression of p53 during the acute phase of anti-cancer therapy has been suggested as a therapeutic strategy to avoid these severe toxic events.
With an eye to this therapeutic strategy, the scientists at Quark Pharmaceuticals have disclosed an invention related to a pharmaceutical composition containing a double-stranded oligoribonucleotide compound, which down-regulates the expression of a human p53 gene. The patent discloses a method of treating a patient suffering from alopecia, acute renal failure or other diseases induced by chemotherapy or radiotherapy in which temporary (reversible) inhibition of p53 activity is beneficial. The present invention also contemplates treating other disorders that are accompanied by an elevated level of p53 polypeptide.
The patent discloses temporary suppression of p53 using the p53 siRNA, such that the novel siRNA molecules protect normal p53-containing cells from chemotherapy or radiotherapy-induced apoptosis. These siRNA molecules may also be used for inhibition of p53 expression in specific cancer cells where p53 inhibition potentiates apoptotic cell death in these cells.