Z Nucleotides and What Ifs…

ORDO News, 2021

A to T, G to C, it’s DNA. We all know this is how it is coded. Adenine (A) to thymine (T), cytosine (C) to guanine (G), it is just how nucleotides pair and make the lovely double helix. The only differentiation is the combination in coding sequences of codons for the 20 amino acids that form the body’s proteins. With research in the last decade, our knowledge may be questioned. There’s a Z!

The Z nucleotide potentially takes the place of the A nucleotide. It would form a T-Z pair that seems to be highly stable due to the three hydrogen bonds as opposed to the two hydrogen bonds of the A-T pair. This is interesting and the Z nucleotide has been found in select bacteriophage viruses or bacteria killer viruses. Further research is still needed to determine if the Z nucleotide can be useful or if it is just a neat anomaly. However, just because the research is still out does not mean we can not imagine how Z-T DNA can be used.

This is the “what if” part, the let our imagination run pretty free part. My mind went right away to the uses of Z genome DNA, forget our present inability to really do anything with it. There are big suppositions and some leaps in this post. If you haven’t noticed already, this approach is slightly different than my usual third person scientific writing. Z genomes are just that interesting!

The first what if is the possibility to program Z nucleotides to specific conditions. For example, program the Z nucleotide to invade and bond to abnormally metabolizing cells, specifically cells that are performing an aberrantly high rate of glycolysis. That would be cancer cells. The cancer cell takes up and metabolizes glucose at an extraordinarily high rate. This new Z genome would create a marker for cancer cells. Granted, there are already tumor marker proteins made at an abnormally high level by cancer cells. So programing Z nucleotides to mark cancer cells would be redundant. Programing Z nucleotides to invade and take over the cancer cells then reprograming the genome of the cell would be the goal. Programing a molecule to adhere to cancer cells has been done. That molecule’s purpose was to program cancer cell death by immune response. It “erased” cancer’s ability to bypass the natural microphage’s phagocytosis. However, the Z nucleotide would not operate that way. It would operate as an off switch.

This is where then next “what if” comes into play. The big “what if we could get Z nucleotides to bond to cancer cells and form Z genome cells” is the first step with a follow up step of “let’s turn off all the Z genomes” in this organism. One of the big issues in current cancer treatment is that the chemotherapy is incredibly destructive to all cells not just cancer cells. It prioritizes cancer cells by targeting the metabolic processes cancer cells use. Chemotherapy drugs are taken up by cancer cells at a high rate due to the glucose scavenging that cancer cells do. But is still leaves healthy cells to take up lesser amounts and still suffer damage. If Z nucleotides bonded to cancer cells using metabolic markers and created Z genome cancer cells, cell death could be programed using the Z genome as the target. So, what if we could program apoptosis of only Z genome cells? Z genome cancer cells would be the only target and the only cell to suffer. It would be the “shut off switch” to cancer.

There is quite a bit of hypothesizing on genetic mutations we have not yet achieved. The uses of an “off switch” would not necessarily be confined to cancer. If we could program a true “off switch” to COVID, I am sure we would. However, programing DNA in select cells to be able to manipulate and terminate specific disease states would be an interesting avenue to investigate. I think it would be just plain neat. Or we would end up in an “I Am Legend” kind of situation…