One of the primary issues with chemotherapy and radiation is that they are not selective -- they kill the good cells along with the bad. It is thus very desirable to create a system for narrowing these treatments’ effects to cancer cells exclusively. Other applications of this siRNA technology include treatment of acute renal failure, which is characterized by rapid deterioration of renal function associated with apoptotic cell death in the kidenys, and other conditions in which p53 is activated as a consequence of a variety of stresses associated with injuries including burns, hyperthermia, myocardial infarction, stroke, and ischemia. Temporary p53 inhibition using the siRNA molecules can be therapeutically effective in reducing or eliminating p53-dependent neuronal death in central nervous system, brain and spinal cord injury; the preservation of tissues and organs prior to transplanting; preparation of a host for a bone marrow transplant; and reducing or eliminating neuronal damage during a seizure. In addition, the p53 gene plays a role in cell aging. In particular, morphological and physiological alterations of normal tissues associated with aging may be related to p53 activity. Senescent cells that accumulate in tissues over time are known to maintain very high levels of p53-dependent transcription. p53-dependent secretions of growth inhibitors by senescent cells accumulate in aging tissue. Thus, the siRNA molecules disclosed in this patent may also be used in suppression of tissue aging.
Since long-term p53 inactivation can significantly increase the risk of cancer, the inhibition of p53 using the molecules is temporary. This may be a difficult balance to achieve, however, and therefore raises concerns that, in attempting to avoid the side effects of cancer treatments, the patient will only increase his risk of cancer. This switching off and on of the gene must therefore be well regulated before it is made available to the public.