We're a long way from effective gene therapy

It seems that the more we learn the more we need to learn. Life appears to be far more complicated than we know. We like to think that we understand the DNA molecule and the transcription process which leads to protein synthesis. We've sequenced the entire human genome and we now know which genes are responsible for many inheritable diseases yet we appear to be far short of the ability to apply our knowledge of genetics to developing effective gene therapies. Ideally, we would like to be able to introduce a drug therapy which actually invades those target cells which harbour the mutant genes and actually rebuild the DNA so that the defective gene becomes normal. I've already explained in my post titled Rethinking genetic engineering why simply addressing a single genetic component could not present an effective gene therapy because the process of protein synthesis involves far greater complexity than merely changing one suspect gene. Other genes and even non-genetic sequences of the DNA molecule are included in the assembly of the RNA template for the purpose of synthesising a single protein. For that matter, the root of some problems may very well not lie with the DNA molecule itself but the methyl groups on the histone proteins within which the DNA is embedded, and to which some of the DNA material is bonded.

Unfortunately, we must admit that the extent of our current knowledge of gene therapy is limited to our ability to actually effect a genetic change in the DNA molecule but that this falls far short of our ability to apply in any practical sense an actual procedure which cures the patient. Furthermore, we are discovering that the idea that just because something seems to work in mice that it should work in humans is essentially flawed. Mice don't always live long enough to present the adverse reactions to gene therapies that are thought to be effective. This reflects the tragic case of two young girls with a severe immune deficiency who were subjects in an experimental protocol and who developed leukemia as a direct result of their treatment. As a result of this event investigating researchers transplanted the treated cells of the first series mice into healthy mice and eventually those mice developed leukemia. The entire process from the treatment of the first group of mice to the manifestation of disease in the second group spanned more than two years.

These reports follow the tragic death of an 18 year old patient who was suffering from arthritis but who was otherwise young and healthy and whose condition was being treated effectively by drug therapies. He took part in an experimental protocol which involved infusion of a gene repair kit via an adenoviral vector. His is the first death attributed to gene therapy.

The community must now sit back and rethink gene therapy strategies. It is clearly apparent that our knowledge at present is incomplete. Only when the entire process leading to synthesis of a defective protein is known and fully understood can we apply effective treatments to eradicate the corresponding disease. And even then the treatment that works for one patient may not be the right treatment for another, even though the same root gene is responsible. When all the factors are known it may be that the vector for treatment involving all of the RNA's components might very well already exist in the form of "smart nanoparticle" carrier bacteria, as discussed in paragraph five of my post titled Bacteria can make us better. These carrier bacteria would in all likelihood need to be custom-made for the patient.