Scientists have developed an improved and relatively simple technique for performing gene therapy, the revolutionary attempt to treat disease by inserting new genes into cells of the human body.
The first human gene therapy attempt, which could be made as early as today at the National Institutes of Health, is to use a complicated method which involves removing cells from the body, introducing new genes into those cells in the laboratory and then injecting the modified cells back into the body. The method is plausible only for a relative few types of genetic disease.
But in a paper in today's issue of Science, a group of University of Michigan researchers present evidence that new genes can be inserted directly into cells in the body, a procedure that will vastly simplify the therapy and broaden its usefulness to many additional diseases.
"We're talking two to three weeks with the old method versus one to two days with ours," said Elizabeth Nabel who wrote the paper with Gregory Plautz and Gary Nabel. All are at the Howard Hughes Medical Institute at the University of Michigan.
Gene therapy has long been envisioned as a possible cure for diseases that result from defective genes. The hope is that by implanting replacement genes -- copies of what the normal gene should be -- the disease can be reversed. Researchers have also proposed finding genes that peform specific disease-fighting functions and inserting them into human cells.
For example, scientists envision that a gene for a substance called tumor necrosis factor, which kills cancerous tumors, could be added to the white blood cells that normally fight tumors. This would give the blood cells an additional weapon against cancer.
The scientific technique involved in this procedure, however, is cumbersome.
Researchers first remove the cells to which they want to add the gene and grow them in a laboratory. Then they splice the gene into the genes of a type of virus that inserts its genes into whatever cell it infects.
The virus is then allowed to infect the removed cells, splicing the new gene into their DNA. The altered cells are then reintroduced into the body.
Researchers at NIH have received approval to use this procedure on 10 children suffering from an inherited malfunction of their immune systems that leaves them susceptible to infections.
The Michigan researchers report that they took a virus containing a new gene and placed it directly into a pig's artery.
They used a common medical procedure known as a balloon catheter. Two tiny balloons were inserted into the artery with viruses carrying the new gene trapped between them. The balloons were then moved to the spot where the new gene was wanted. In this case, the viruses carried only a gene for an enzyme that turned the infected area a tell-tale blue.
The researchers also performed the same direct gene therapy using what are called liposomes. These are small bubbles of fat enclosing new genes. In this case, the cells absorb the lipsomes in a chemical reaction, taking up the foreign DNA at the same time.
The researchers said this direct gene transfer could potentially allow for the broader application of the therapy, at least in cases where the target cells can be reached by catheter.
Nabel said the new method had not been tried earlier because scientists did not know whether they could introduce new genes into cells at all. So they worked on cultured cells in a dish. Now that the procedure is known to be possible, she said, she and her co-researchers felt it should be possible to transfer the new genes directly into cells while they reside in an intact animal.
"As the field of gene therapy evolves, we are going to get away from the indirect method of gene transfer," she said. "I think we are going to see the field rapidly expand in the direction of direct gene transfer."