Course: SAT 170 Introductory Biotechnology

Unit 7 Reading and Multimedia Assignment

SubTabs

- Unit 7
- Table of Contents (Selected)
- Unit 7 Key Terms (Selected)

Page 6 of 8
Credits

Link: http://www.open.edu/openlearn/science-maths-technology/science/biology/gene-therapy/content-section-0

Attributions: An OpenLearn chunk used/reworked by permission of The Open University copyright © (2013). CC-BY-NC-SA
Reading Assignment: Gene Therapy

1 Genetic medicine: dreams and realities

Genetics can be used in medicine to confirm a previous or make a fresh diagnosis, or predict a disorder likely to occur in future. At the moment, that is often all that can be done. The so-called ‘diagnostic therapeutic gap’ is one immediate problem for us to deal with. When the only options on offer after a genetic test are to terminate a pregnancy, or prepare to deal with the disease as best you can, some of the dilemmas of new genetic knowledge are sharper.

Genetic testing is only the beginning of the effect of genetics on medicine. What about treatment? This unit looks at various ways in which the new knowledge of the human genome will affect how illnesses are treated. These treatments are already getting underway. We look at the one that gets talked about most — gene therapy — but also at other possibilities, which may be more important in the short term. These include using information about a person's genotype to prescribe drugs more closely tailored to their body chemistry.

2 Gene therapy

Gene therapy is often reported to be one of the most hopeful lines of experimentation to grow up alongside the Human Genome Project. If we know so much about all these genes, surely we can use this knowledge to try to treat some diseases in which genes are involved at a fundamental level? But what exactly is gene therapy, and where is the work heading?

Just looking at the two words coupled in the phrase ‘gene therapy’ raises an important ambiguity.

It turns out that it means both. Most of the public debate has been about the former meaning, i.e. correcting or repairing genes, but early applications have focused on the latter meaning. These applications involve using ‘designer’ DNA to tackle diseases that are not inherited – by using altered viruses designed specifically to attack cancer cells, say. Here, the DNA is working more or less like a drug. In fact, many ‘gene therapy’ trials approved so far have been attempts to treat a variety of cancers.

Here, though, we will focus on the first of the two meanings of gene therapy, correcting genes. Some genetic diseases can be tackled by modifying the phenotype, without worrying about how DNA might be involved. Most simply, a multifactorial problem like a cleft palate can be corrected surgically. But for many diseases, such as cystic fibrosis (CF), non-genetic treatments can help to alleviate some symptoms, but so far that is all. So in a single-gene disorder such as CF, the theoretical focus is now on the gene and its product. We begin by focusing on gene products, i.e. proteins, and then consider genes.

The idea of, in effect, treating the genotype, has been around from the 1960s. Since the new technologies of genetic manipulation came into widespread use in the 1980s, many trials of gene therapy have been carried out on humans. Despite high hopes, few have yet shown clear benefits to patients. At the turn of the millennium, it looked as though gene therapy would be more complicated, and take longer to deliver, than was thought 10 or 20 years previously. On the other hand, it may turn out that the techniques now being tried are superseded by more successful ones as our knowledge increases. The remarkable pace of technical developments suggests that it would be unwise to discount changes to human genes in the medium term. The rest of this chapter considers some of the possibilities and problems to look out for.

3 Somatic gene therapy

There is a distinction between somatic cells, those making up almost all of the body, and germline cells, which are the eggs and sperm and the cells that produce them. Somatic gene therapy is the transfer of genes into the somatic cells of the patient, such as cells of the bone marrow, and hence the new DNA does not enter the eggs or sperm. The genes transferred are usually normal alleles that could ‘correct’ the mutant or disease alleles of the recipient.

The technique of somatic gene therapy involves inserting a normal gene into the appropriate cells of an individual affected with a genetic disease, thereby permanently correcting the disorder.  In some cells, the gene or genes become inserted into a chromosome in the nucleus.

The target cells might be bone marrow cells, which are easily isolated and re-implanted. Bone marrow cells continue to divide for a person's whole life to produce blood cells, so this approach is useful only if the gene you want to deliver has a biological role in the blood. Delivery of a gene that has a biological role in, say, the lungs, muscle, or liver would have to occur within those target organs. In many cases, accessing the appropriate tissue or, if the gene is required in multiple tissues (e.g. muscles throughout the body) ensuring it can be delivered where it is needed, is a major problem.

In general, current efforts to treat disease by somatic gene therapy do not pose any novel ethical issues, provided there is proper enforcement of informed consent in trials. There is concern, however, about where the successful development of techniques for germline gene therapy might lead.

4 Germline gene therapy

Now that in vitro fertilization – bringing eggs and sperm together outside the prospective mother's body – is an established technology, the possibility exists that genes could be altered in eggs or sperm, or in a very early embryo. The obvious advantages of germline gene therapy are that the cells are accessible (because they are outside the body), so gene delivery is less of a problem than it tends to be with somatic cells; and the inserted gene (or genes) would be present in all the cells of the person so treated because it would be transmitted to progeny cells during growth and development.

Until recently, there was widespread agreement that germline gene therapy in humans should be ruled out. It is currently (early 2005) banned in the UK. It is not possible to predict where in the genome a newly inserted gene might end up, and this poses unknown risks of causing new mutations, or otherwise disrupting normal gene functioning. Even if these hazards could be removed, there are new ethical problems that could appear with serious development of germline therapy. These include how to decide which genetic alterations to permit. Some would clearly be aimed at correcting harmful mutations, but others might be considered enhancements, rather than treatments. Sometimes, it may be hard to tell the difference.