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Decoding the genome is only a third of the way

This week the countdown began towards a real revolution in the medical treatment of hereditary diseases and cancer, with the announcement of the completion of the first draft of the mapping of the human genome. But there are still many technical and ethical problems that must be solved before the application of gene therapy

This week it was officially announced that the first draft of the mapping of the human genome had been completed,
The future project will change our lives from end to end. Gene discovery
new ones, finding the location of known genes and understanding how the genes function
will bring about a revolution in medical treatment. Gene therapy is one of the leaders
in this upheaval. The field recently suffered a blow with the death of one of the trial participants
A clinic where genes were inserted into patients with hereditary liver disease. As a result
The US Food and Drug Administration ordered the trials to be stopped
The clinical in the experimental group. About a month ago, the administration ordered to stop
The clinical trials in inserting genes into the heart muscle, after the condition of
One of the participants of the experiment. The US health authorities are now examining the
Gene therapy programs throughout the country. In contrast, in April reported
French team on success in creating an active immune system in two babies
who were born without an immune system.

Gene therapy promises a lot: replacing damaged genes, treating cancer cells
By inserting genes that code for proteins designed to destroy the
the tumor, to insert genes into nerve cells that will function in curing degenerative diseases
of the nervous system, to transfer genes to a damaged heart muscle that will restore its function,
to inject genes into cells infected with the AIDS virus that will lead to its elimination and more.
These promises are now being tested. Will the gene therapy realize the
The hopes planted in him? And what will be the direction of his progress with the completion of the genome mapping
the human?

About eight years ago, in the Department of Pulmonary Diseases of Maryland, USA,
A revolutionary experiment in a cystic fibrosis patient - a fairly common hereditary disease
which causes the destruction of lung tissue and death at a young age. The patient was infected with the virus
Attacking lung tissue, a virus in whose genetic material a human gene has been implanted.
The transplanted gene was supposed to produce the defective gene products in the patient.
The experiment failed, because the patient's immune system rejected the viruses
that were injected into his body, but he marked a starting point in curing diseases through
Transferring healthy genes that will function in place of the damaged genes.

In the nineties, gene therapy gained momentum. The researchers knew that to
To succeed in the task, three conditions must be met: Isolate the intended garden
replace the damaged gene; find a system that will carry it into the cells,
And inside the cells to make sure that the gene joins the appropriate place in the DNA. it was clear
Because the key to success is to find a suitable carrier who will be able to transfer the genes
safely and effectively to the patient's cells. The most suitable candidates were
The viruses that enter the cells and multiply in them. through genetic engineering
The genes responsible for their violence are removed from the viruses and planted in the material
their genetics the genes intended for transfer.

Additional means of introducing genes are liposomes - tiny fat bubbles
in which are packed the genes intended for the direct launch and injection of molecules
DNA where the necessary genes are located. In these two methods are absorbed
The genes are less efficient and they are expressed for a short time

How is the gene transfer done? One way is an extracorporeal method: they take it out
Cells from the damaged tissue, in the laboratory they are brought into contact with the carrier, and after
that the carrier penetrates the cells inject the cells back into the body. according to the method
The second, intracorporeal, injects the carrier directly into the damaged tissue.
The choice between the two approaches depends on the nature of the disease.

Most experiments in gene therapy are done today in cancer patients. One of the ways
is to damage the system of creating new blood vessels that supply him with oxygen and food.
In many centers around the world, the cells in these blood vessels are injected with coding genes
to proteins that inhibit the formation of new blood vessels. The assumption is that at
Adults almost do not form new blood vessels, so they are the first to be damaged
From the insertion of the genes, the tumor cells are constantly gathering blood vessels around them, vessels
blood they need for their development. In mice they were able to delay this
Development of cancerous tumors, and now preparations are being made for clinical trials in men
A person.

Another way is to strengthen the immune system against cancer. successful crops
develop partly due to the inability of the immune system to fight them,
Because the tumor cells "hide" their antigens - them
The proteins that stimulate the immune system response. in the experiments being done
These days, cancer patients are injected with DNA that codes for the antigen that distinguishes the
the growth. The immune system reacts against the antigen and produces substances
which work to eliminate cancer cells. Experiments are already being done on humans
clinical with this method.

The fight against cancer is also done by repairing the damaged genes involved
in illness One of them is the cancer suppressor gene P-53, which is in 50% of tumors
Cancer is flawed. Using a suitable carrier, the cancer cells are injected
The normal gene, on the assumption that if it is found in a large amount it will aid in healing
the cancer. In other experiments, coding genes are injected into the tumor cells
For special proteins that strengthen the immune system and help it fight
in crops.

"Strengthening the immune system is the right direction in the fight against cancer," he says
Prof. Zelig Ashchar from the Department of Immunology at the Weizmann Institute. "I am
I believe that in the future we will be able to vaccinate before the disease appears. Some are already known today
Genes that make it possible to locate people from risk groups that are likely
high to get sick, breast cancer for example, or colon cancer. Genome mapping
Man will help find additional risk groups through new genes that will be discovered.
This way we can vaccinate and prevent the outbreak of the disease at a young age."

Gene therapy also enters the field of heart disease treatment. One of the methods
The subjects are injected into the heart muscle cells instead of blocking the genes
which encode proteins that stimulate the formation of new blood vessels. That's how you wake up
Creation of blood vessels bypassing the blocked area.

More than 4,000 patients have participated in gene therapy trials in the past decade,
But despite the intensive studies, the results are ambiguous, and no one is sick
Still not healthy. The recently reported experiment - gene transfer of a system
The vaccination for the two babies in France - raises many hopes. the researchers
Using a virus, the appropriate genes were injected into the stem cells in the bone marrow
responsible for creating the immune system. Today, one year after the treatment,
The babies are developing nicely and do not need medication. Hemophiliacs too
They benefit from the gene therapy. through viral vectors that transmit
The cells of their bodies have the genes responsible for creating the factors that are missing for the need
Blood clotting.

"Today we have the tools for gene therapy, but it still cannot be implemented
them in humans mainly because of safety issues", says Ashhar. for example,
A carrier belonging to the group of AIDS viruses that transfers the genes very efficiently
most. Even though genetic engineering methods can remove the genes from it
The violent, it did not enter the phase of clinical trials in humans because
The special caution required in using this carrier and because of ethical issues

"We still haven't resolved one point," says Ashhar. "Even when you get to the cell
That's right, there is still no method that verifies that the garden goes into the right place
in the DNA, and when the gene settles in a random place it can cause events
Unwanted like cancer development. Mapping the genomic sequence will identify regions
such and will prevent it."

"There is no doubt that gene therapy will revolutionize medicine, the question is when," he says
Prof. Amos Fant from the School of Medicine at the Hebrew and Hadassah University.
"One of the problems is that in the last decade many were optimistic. they are not
Take into account some seemingly technical problems, but they actually are
hindering the medical revolution brought about by gene therapy. One of the problems
Centrality is the ability to transfer genes efficiently into the cell. the carriers
that use them are primitive and create side effects. hundreds
Articles are published on the matter every year, but they are not actually translated yet
is beyond the door."

Many interests drive this field. Commercial companies spend
Patents on methods for introducing genes into cells. Many researchers apply for funding
Commercial companies, because the work methods are expensive and they are not always able to finance
Experiments from public sources, and the commercial companies recruit the
The media for quick publication of results for the purpose of raising funds in the stock market.

"We are at most a third of the way today, and in my estimation, from all the noise
The big one will be left with about ten uses that will bring about the revolution", Pent concludes.
{Appeared in Haaretz newspaper, 30/6/2000{

* The knowledge site was until the end of 2002 part of the IOL portal of the Haaretz group

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