PR for HIV Vector Use from NY Times
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January 19, 1999
Scientists Enlist H.I.V. to Fight Other Ills
By ANDREW POLLACK
SAN DIEGO, Calif. -- In a bold but potentially frightening
effort to turn one of the world's most
virulent killers into a cure, scientists and biotechnology
companies are trying to tame the AIDS
virus and harness it to treat disease.
The scientists say they have stripped the human immunodeficiency
virus of its ability to cause disease,
while leaving intact its ability to infect human cells. Such a
crippled virus, they say, could be used to
deliver genes into human cells for gene therapy.
Several university scientists and biotechnology companies hope to
clinical trials using the modified HIV viruses to carry genes that
they hope can
be used to treat diseases such as cancer and hemophilia. At least
will even be made to use the modified HIV, the virus that causes
AIDS, to treat
"It would be ironic to cure AIDS with the AIDS virus," said Dr.
Verma, a professor at The Salk Institute for Biological Studies
here, who has
pioneered the effort to harness HIV for gene therapy. But he added,
"There is a
saying that diamond cuts diamond."
Verma and others involved in such research say it is virtually
anyone treated using the crippled HIV could get AIDS as a result.
carrier, which is known as a vector, not only is missing the HIV
genes that cause
disease but also lacks the ability to replicate and spread in the
body, they say.
But some experts note that in rare instances, disabled viruses can
recombine with genetic material
from other viruses or from the person's own cells to regain the
ability to replicate. And even if the
actual risks are low, patients are likely to be afraid, and
regulators cautious, about injecting patients
with even a modified AIDS virus.
"It's a human pathogen that's caused a terrible pandemic, so one
needs to be thoughtful about using it,
even in a crippled form," said Dr. Eric Poeschla, an assistant
professor of medicine at the University
of California at San Diego.
The Food and Drug Administration, whose approval is required for
gene therapy trials, agreed.
"There are a number of scientific questions and safety issues to be
addressed before any of that could
go forward," Dr. Philip Noguchi, the director of the agency's
division of cellular and gene therapies,
said in an interview. "We don't quite know what we should be
concerned about because the biological
understanding has not been developed yet."
The National Institutes of Health held a meeting of experts last
March to explore the use of HIV
vectors for gene therapy, which involves inserting genes for a
particular function into a patient's cells.
But Noguchi said a wider, more open public hearing would be held
before his agency would consider
approving the first such trial. "The public hasn't really weighed
in with its own opinion," he said.
It is the very infectiousness of HIV that makes it attractive for
gene therapy, which so far has not lived
up to its expectations. People with hemophilia, for instance, have
an inherited genetic defect that
prevents them from making a crucial protein needed for blood
clotting. But if enough of the patient's
cells could be provided with the proper gene, the patient could
manufacture his own blood clotting
To deliver the genes of interest, scientists generally insert them
into debilitated viruses, because
viruses spread by delivering their own genetic material into the
cells of their target. But gene therapy,
which has been tried for about a decade, has in general failed
because it has been impossible to
deliver enough of the genes, and get them to work long enough, to
make enough of the required protein.
In many cases the viral gene carriers are attacked and destroyed by
the body's immune system. Some
of the viruses used so far allow for only transient production of
the protein because they do not
incorporate the genes they carry into the chromosomes of the target
One of the most commonly used vectors, derived from mouse leukemia
virus, can deliver genes into
chromosomes, where, it is hoped, they will operate for a long time.
But this vector can do this only
when cells are dividing, making it difficult to treat diseases in
the brain, liver, heart and other organs
in which cells divide rarely if at all. And a promising new vector,
based on adeno-associated viruses,
appears safe and somewhat effective, but is limited in the size of
the genes it can carry. HIV, on the
other hand, is both cunning at evading the body's immune defenses
and can carry large genes. Most
important, it is one of a small class of viruses, known as
lentiviruses, that can incorporate genes into
the chromosomes even of nondividing cells.
"Lentiviral vectors are really a new hope in the field of gene
therapy," said Dr. Philippe LeBoulch,
assistant professor of medicine at Harvard University and chief
scientific officer of Genetix
Pharmaceuticals Inc., a privately held Massachusetts company
planning to use HIV-based vectors in
Verma's lab has used the vector to incorporate genes into the
brain, liver, muscle, bone marrow and
retinal cells of rats or mice. The genes seem to function for months.
Still, others say, it is not clear whether the HIV vectors will be
efficient enough to make gene therapy
work. "They are still going to have to struggle to get genes into
people, even using an HIV vector,"
said Poeschla of the University of California.
Besides being infectious, the AIDS virus has been extensively
studied, so that scientists know how to
modify it. "We know every nucleotide down to the last base," Verma
His laboratory's latest vector removes six of the nine genes in the
AIDS virus. One big change that is
required is that of the virus' protein coat, which determines which
cells it can attach to. The AIDS
virus mainly infects certain white blood cells known as T cells. So
scientists have replaced the HIV
protein coat with that of a cattle virus that seems to be able to
infect many different types of human
The only genes taken from the HIV itself to make the vector are
those that govern the process by which
the viral genetic material is incorporated into the chromosome of
the target cell. These genes are put
into cells known as packaging cells, which produce the actual
The vectors themselves -- the particles that would be injected into
a patient -- contain the viral
proteins needed to incorporate the therapeutic gene into the
patient's chromosomes, but they do not
contain the genes that direct the creation of those proteins. So
after it incorporates the gene into one
cell, the viral particle cannot go on to direct the cell to produce
Copyright 1999 The New York Times Company