every move you make, every bond you break

Do you ever get the sense that some people are using that extra little bit of brain capacity that others don't? Or that they are simply on more than others are? If you have never felt that way, I would advise that you meet Saheli some time. Her brain goes to 11, people.

She may have been indulging me by asking a question about oncogenes, and whether we can figure out how to turn them off. Of course, I failed spectacularly at explaining it in any kind of coherent manner, especially when I launched into a really poor explanation of antisense technology. I shall try to make amends by attempting to explain it again here.

Genes live deep in your cells. They call the shots in the body from their central command center in the nucleus. An oncogene is simply a gene that has gone bad. As a result of a mutation, a normal gene is altered such that it sends the wrong commands. These commands inevitably lead to your cells thinking it is time to proliferate, and that is how the big C gets its start.

Saheli asked if oncogenes can be turned off. Directly or indirectly, most targeted anticancer therapies are trying to do just that. The most direct method of turning off an oncogene is the use of antisense. How does an oncogene, or a gene in general, really command a cell? Well, genes are DNA. It is easy to think of DNA as a blueprint for our body, and something that is passed on during replication, but it is important to remember why it runs the show.

DNA makes RNA, and RNA makes proteins. If you have bad DNA, you have bad RNA, and all of sudden, you may have more protein than you wanted. With oncogenes, more often than not, this excess of protein then signals cells to start dividing out of control. DNA is the boss, RNA make up middle management, some proteins make up supervisors, while other proteins are worker bees. Everything is connected and signalling each other. It is actually a little ovewhelming to think about how interrelated everything in just a single cell is.

Antisense cuts through the red tape and goes straight for the boss. By creating a sequence of complementary nucleotides, it is possible to selectively block the bad DNA from making bad RNA. The antisense molecule has got your number, bad DNA! It is such a beautiful concept that it can seem like the silver bullet cure to cancer. Unfortunately, there are weaknesses. In order to get to the bad DNA, an antisense molecule has to get inside the cell and then into the nucleus. Since it is a string of nucleotides, however, getting it past all of the body's usual clearance mechanisms is nearly impossible. Furthermore, even assuming you can get the molecule to stick around, there is the additional challenge of getting it to enter the cancer cell selectively, and then into the nucleus. I am tired just writing about how far this little hobbit has to travel to destroy the ring.

The situation, as always, is not hopeless however. Since research has shown that injecting a nucleus directly with antisense molecules can turn off the oncogene, it is too important an approach to simply discard. Instead, research is being conducted to see if these antisense molecules can be harnessed with delivery systems, systems that will protect the molecules from being chopped apart by the body, and getting them specifically into a cancer cell. But those are topics for another day.

Hmmm. Unfortunately, I am not sure that was any better an explanation than what I came up with last night. Look on the bright side- at least I am not blogging about the gender divide today, and it is Friday.