RNAi: ARE THESE MOLECULES REALLY SO PROMISING?

RNAi: ARE THESE MOLECULES REALLY SO PROMISING?

RNAi molecules may lead to much new knowledge of gene function, but therapeutic applications seem less promising.

History is full of new discoveries, many of which, at the time, seem to open doors that offer panaceas for unlimited benefits. These advances, as well as the more mundane decisions which we all have to make, need to be analyzed in three stages. First is the elation of wondrous possibilities that excite us and make us want to embrace the possibilities fully and immediately. Second, however, comes the time of contemplating the downsides, risks, and limitations. Third comes the time of melding these two so that we get a balanced decision.

RNAi, in my first posting about it, was slanted to the first of these three steps – the exhilarating joy of a new discovery and the credit due the
discoverers now being honored. Let’s look at the second stage. Controlling genes can be conceived in two ways. First is the possibility that the gene (DNA) in a particular chromosome of all the cells in a human body can be blocked or destroyed. It follows then that a new and better gene could be inserted to replace the bad gene. This effect on DNA is not the case with RNAi uses, as far as we know now, because neither the original gene is significantly affected nor is the insertion of another gene simple when a defective one is still acting. Why?

The current explanation for the function of RNAi molecules is that they block the expression products from a given gene. That is, from the gene’s DNA, a messenger RNA molecule is produced and moves from the nucleus into the cytoplasm where it is used on ribosomes to control the assembling of amino acids in the proper sequence for a specific protein. RNAi intercepts the messenger RNA, binds to it, and inactivates or destroys it. The DNA is not affected by the RNAi
molecules.

RNAi molecules are exciting for two reasons. First, they can be used for research on what a particular gene does functionally. In this, RNAi is a powerful, highly useful tool and holds great promise. The other function is that RNAi molecules can cure or alleviate diseases. Here the promise is more limited. Suppose, for example, that a cancer oncogene has been triggered and lead to the
formation of a tumor. Then an RNAi molecule is used to suppress the gene. Since it is unaffected by the RNAi molecule, the gene has continued generating its messenger RNA during RNAi treatment. As soon as RNAi therapy is stopped, this
continuing supply of messenger RNA resumes, and its damaging function resumes. Therefore, you can see that treatment of the oncogene may need to be continued on a permanent long-term basis. This regimen may sound like a great idea to a
pharmaceutical company, but is a nightmare for patients and third-party payers since RNAi molecules will likely to be expensive to produce and market.

So let’s not get too carried away by the advent of cures for all the disease processes and congenital defects we can list. Rather, let’s realize in the third stage of considering RNAi, that another treatment leading to permanent blocking will be required. That will not likely be RNAi, as we now know it.