Q: Gene therapy is an experimental technique that allows doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. These implanted genes take over for missing or malfunctioning genes. I understand that genes are in a person’s DNA, which is a part of every human cell. How can a gene be injected into a single cell and be therapeutic? Wouldn’t the gene need to injected into every cell?
Bob Johnson, of Collinsville
A: How many times have you been so busy that you wished you could split yourself into two (or more) people to finish all the work piling up on your desk?
Obviously, you can’t. But cells can. They do it all the time. One cell becomes two becomes four becomes eight, etc. That’s how a sperm and egg get together to ultimately produce an average adult human with 37 trillion cells, according to an estimate in a 2013 issue of the Annals of Human Biology. And, if everything goes as it’s supposed to, each new cell contains an identical copy of the 20,000 to 25,000 genes on your 23 chromosomal pairs.
So once you successfully insert a gene into the DNA of one or more cells, it will (hopefully) start telling the body to immediately begin pumping out the RNA or protein product it is meant to produce. Then the cells with the modified DNA will keep dividing, ever increasing the number of genetic factories able to make the desired substance. Moreover, the new gene often has to be placed only in the cells of a specific organ such as the brain or liver. So there’s no reason you have to get it into absolutely every cell initially.
OK, that’s one problem solved. But that leaves your more basic question: How in the world do you go about incorporating a new gene into these fundamental building blocks of life in the first place?
It would be nice if you could just stick it into a hypodermic and shoot it into a cell or two, but you can’t. A gene inserted directly into a cell usually will not function. Instead, scientists have had to devise ingenious and complex ways to make these genes become a working part of their new hosts.
In a way, it’s sort of like being in New York and wanting to see a concert in London. Without boarding a ship or plane, you’d never make it to the event on your own.
The same is true of that gene. It, too, needs special transportation to sneak into the cell and enter a person’s DNA or, at least, a cell’s nucleus. But instead of a Boeing 747, scientists often put it in a virus. Anyone who has ever had a cold or the flu (which is probably everyone) unfortunately knows how efficient Mother Nature has become over billions of years at getting viruses to invade cells. Viruses often offer the bonus advantage of targeting specific types of cells. That’s why scientists have chosen them to be their UPS delivery vans to get genes into cells. (They’re called “vectors” in scientific lingo, but that sounds so stuffy.)
Now, I know what you’re probably going to say. A virus? You’re going to give people an illness before (hopefully) making them better? Hey, unlax. Scientists also have found a way to modify these viruses so they cannot cause disease directly even while performing their duty of getting the gene to where it’s needed.
I say “viruses” because, so far, no one virus can be used as a vector to treat every disorder. Each gene therapy vector must be customized to meet the needs of the particular problem being addressed. So scientists must be sure each vector can target the right cells, integrate the gene into those cells, activate the gene once it’s there and avoid any harmful side effects.
Some types of viruses can integrate their genetic material (including the new gene) into human DNA. These are called retroviruses. In other cases, modified adenoviruses (the kind that cause the common cold) are used to simply get the gene into a cell’s nucleus, but not into a chromosome.
Incorporating the gene into cells can be done two ways — in the body, either through injection or IV, or in the laboratory. In-the-body therapies often take advantage of a virus’ desire to infect certain organs. For example, researchers are using it to test new Parkinson’s treatments because only part of the brain is targeted. Because adeno-associated viruses target the liver, where clotting factors are added to the blood, viruses may prove useful in hemophilia treatments involving genes.
In out-of-body therapies, doctors take a patient’s blood or bone marrow and extract immature cells. They then inject a gene into these cells and shoot them back into a patient’s bloodstream. The modified cells then travel to the bone marrow, mature and start dividing rapidly to replace the body’s own defective cells.
Such therapy already has been used to treat severe combined immunodeficiency — SCID or, as it is more popularly known, boy-in-the-bubble syndrome. More than 30 such children have been treated, and more than 90 percent have been cured of the disorder. That’s a distinct improvement over the 50 percent mark usually achieved by bone marrow transplants alone.
Other delivery systems are being investigated as well. Because viruses are limited in the amount of genetic material they can carry, non-viral vectors such as a DNA molecule known as a plasmid and synthetic vectors called virosomes are seen as possible alternatives to increase the amount of genetic materials doctors could introduce to the patient’s body.
But such therapies are still in their infancy and certainly no magic bullet. Even when using weakened retroviruses, scientists have found the new gene sometimes becomes spliced into the DNA in a way that disrupts other genes and causes leukemia. At least five of the SCID children developed this complication, so even while four of them beat their cancers, the work for safer therapies goes on.
Name the foreign-born actor who twice was nominated for an Academy Award as best actor when he played the same character in two different films.
Answer to Friday’s trivia: If you’re looking for the worst actor or actress in the past 35 years, you’d have a hard time finding one more awful than Sylvester Stallone, according to the Golden Raspberry Awards people, who annually bestow their Razzies on the dregs of the film world. Since 1981, when the awards were first given, Stallone has been nominated 19 times with six “wins” — not counting a special Razzie for worst actor of the 20th century. Named worst female actress of the century was Madonna with nine nominations and seven Razzies.