Genes and Even More Things 3          original text from New Scientist June 10, 2006


Gene scissors
1) Adding zinc fingers to DNA-cutting enzymes called nucleases creates "molecular scissors" capable of cutting a strand of DNA at a specific point (see Diagram). Why would you want to do that? The answer lies with the mysterious process of homologous recombination, which is carried out by repair enzymes. Several teams have shown that if you cut the DNA you want to alter at the same time as adding the replacement version, you force the repair enzymes into action and enormously increase the rate of homologous recombination.

2) In June last year, Sangamo reported that it had used custom-designed scissors to correct the mutation that causes X-SCID in 18 per cent of bone marrow cells taken from patients (Nature, vol 435, p 646). The paper created quite a stir. "The Sangamo group has achieved truly remarkable efficiencies," Dana Carroll of the University of Utah in Salt Lake City told New Scientist at the time.

3) Sangamo has since proved its result was not a one-off by taking human immune cells and using molecular scissors to make them resistant to HIV (New Scientist, 2 July 2005, p 14). Repopulating a patient's immune system with these cells might keep AIDS at bay indefinitely. "I think the potential is enormous," says Matthew Porteus of the University of Texas, Dallas, one of the authors of the X-SCID paper.

4) Sangamo is focusing on gene therapy, but molecular scissors also look set to become a key tool in genetic engineering. In 2003 Carroll's team showed that they could be used to genetically engineer fruit flies, and has since done the same in plants.

5) Promising as they are, however, molecular scissors are not the full answer. One problem is that they can cut DNA at sites other than the target, causing double-strand breaks. The breaks can kill cells but this won't be a huge issue as long as the scissors are used to treat cells outside the body prior to reimplantation, as Porteus envisages.

6) More of a worry is that if the breaks are repaired incorrectly, cells might turn cancerous. As no cells modified by scissors have yet been reimplanted in animals, it is not yet clear how big the risk is. "My view is that the problem is solvable," says Porteus. There are other limitations though. For instance, the bigger the piece of DNA you want to insert, the less efficient molecular scissors become.

7) The ideal solution would be to combine the virtues of both approaches - the ability to target any desired sequence, as Sangamo can, and the ability to add or remove very large chunks of DNA, as can be done with recombinases. To achieve that means finding a way to alter recombinases to bind to the specific sequence you wish to target. That is not easy, says biochemist Marshall Stark of the University of Glasgow in the UK, because recombinases are far more complex than the nucleases in Sangamo's scissors. Nevertheless, his group has already succeeded in altering one recombinase to target a sequence it would not normally recognise. Getting a recombinase such as phi C31 to target any sequence is just a question of time, he says.

8) The efforts of researchers like Stark and Calos are slowly ushering in a new era in genetic engineering. Soon the extraordinary feats biologists take for granted in mice will become possible in many other species, including our own. Twenty or so lives have already been transformed; millions more are awaiting their turn.

Task 1 Comprehension: Answer the questions below. Remember to use your OWN WORDS!!!
Q1
 This section of the article is called ‘Gene Scissors’. Why do you think the author chose this title?
A
Q2
 What are the advantages of using gene scissors?
A
Q3
 What are the drawbacks?
A
Q4
 What course of action does the author recommend in the second last paragraph?
A
Q5
 What is the author’s conclusion?
A

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