A Proposed Solution

How can we prevent damage to p53? Well, in practice it is really quite difficult to predict when a gene will get damaged. As mentioned on the cancer main page, there are quite a lot of things that can happen to DNA to damage it. Environmental factors can always damage DNA, and it can also get damaged in the process of being replicated. There is not really one good way to prevent DNA damage- meaning there is not a good way of preventing p53 specifically from being damaged.

One possible route to preventing cancer is to reduce the instances of Li Fraumeni syndrome- a rare inherited genetic disorder in which both copies of the p53 gene (one from each parent) are damaged. People with Li Fraumeni Syndrome are more prone to developing certain kinds of cancer, such as breast cancer, osteosarcoma (a type of bone cancer), and soft tissue sarcoma (cancer that affects soft tissues such as muscles). Through genetic sequencing using modern technology (such as the kind mentioned by the National Human Genome Research Institute) we can watch DNA polymerase as it replicates a genetic sequence using high speed cameras and dyes for specific nucleotide bases. If that sequence is found to be damaged (in the case of p53) a gene editing tool such as CRISPR-Cas9 could be used to cut out the damaged sequence of DNA and replace it with a non-damaged p53 gene.

Genetic editing using CRISPR-Cas9- a new gene editing technology that is still in the process of being developed and tested- may be a viable solution to finding and replacing damaged DNA in embryos, specifically the embryos predisposed to Li Fraumeni Syndrome.

How does CRISPR-Cas9 work?

An enzyme called Cas9 is able to act like a pair of DNA scissors, cutting a strand of DNA at predetermined points in its sequence.

A strand of guide RNA (gRNA) is created to match a certain sequence of DNA (which has been previously determined- for our purposes we will be finding the damaged p53 sequence) This gRNA will bind to the DNA at the correct point in the sequence, signaling Cas9 to cut at the start and end of the indicated sequence.

Once the enzyme has cut the DNA, the cell’s own DNA repair machinery can come in and try to repair the damage. Scientists can use the DNA repair machinery to introduce the desired changes to the DNA of the cell.

Other solutions:

Another answer to the cancer problem may lie in gene therapy- introducing genetic material into the host cells using a vector such as a retrovirus. A retrovirus is able to enter the nucleus of a cell and integrate its DNA into the chromosome of the host cell- for our purposes we would pass the retrovirus a copy of our undamaged p53 gene and either inject the virus intravenously into the patient or expose a sample of the patient’s cells to the virus and reinsert them back into the patient. This technique has promise but it is still under development, somewhat dangerous, and the subject of many ethical concerns. As a method to fight cancer in adults, it has promise.