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----- Original Message ----From: <[email protected]>
To: <[email protected]>
Sent: Saturday, April 06, 2002 5:22 PM
Subject: Trial of Gene therapy for cystic fibrosis
Novel Gene Therapy Approach In 1st Human Trials
April 2, 2002
http://genomics.biocompare.com/gnews.asp?id=4426
[The type of collaborative effort between researchers, clinicians and
industry that is discussed in this article is what is needed to bring a cure
to FD in our children's lifetime. ]
A 33-year old cystic fibrosis patient underwent the first gene therapy trial
today using a novel approach to fight a deadly genetic disease that affects
more than 30,000 Americans. The researchers include a team from The Research
Institute of University Hospitals of Cleveland, its Rainbow Babies & Children’
s Hospital, Case Western Reserve University School of Medicine, and
Copernicus Therapeutics Inc., developers of the novel gene transfer system.
“Over the last decade, there have been various attempts to transfer healthy
genes into the cells of the airways of cystic fibrosis patients,” explains
primary investigator Michael W. Konstan, MD, Director of the LeRoy Matthews
Cystic Fibrosis Center at Rainbow Babies & Children’s Hospital, and associate
professor of pediatrics at CWRU School of Medicine. “Most of these trials
have involved the use of a viral vector, attaching the healthy gene to a
virus that will invade cells. Unfortunately, the virus itself has caused
troublesome inflammation in the study patients.”
For more than a decade, UHC/CWRU researchers have explored alternative
methods to viral vectors. Their work led to a patented approach produced by
the Cleveland-based biotechnology firm, Copernicus Therapeutics, Inc. They
developed a way to “compact” or tightly bind strands of DNA so that it is
tiny enough to pass into the cell and then into the nucleus. Once inside a
cell, researchers hope that the DNA will produce the normal version of the
protein needed by cystic fibrosis patients.
Thirteen years ago, scientists discovered the cystic fibrosis (CF) gene. This
defective gene upsets a delicate salt/water balance in the lungs. At the crux
of the process is a protein, produced by the CF gene, which controls the flow
of salt and water in and out of cells. In CF patients, this protein does not
operate normally in the cells that line the airways. In turn, the airways
accumulate thick and sticky mucus. Bacteria proliferate in the mucus and
cause chronic infections that permanently damage lungs.
Under the direction of Dr. Konstan, the research team delivered the healthy
gene into CF patient Robert Calhoun in a saline solution dripped slowly into
his nasal passages. Investigators monitor the salt transport in his nose,
called “nasal potential difference,” as a barometer of the procedure’s
success. “CF patients have a markedly abnormal nasal potential difference,”
Dr. Konstan says. First, through biopsies of nasal tissue, researchers will
determine whether the healthy gene was “taken up” by the cells. Then, if the
DNA produces enough protein, there should be a change in the transport of
salt and water in and out of the cells, which can be measured by the nasal
potential difference test.
“This is a terrific example of the style of translational research that goes
on at The Research Institute, bringing advances from the lab to improvements
in health care”, commented Huntington F. Willard, Ph.D., President and
Director of the Research Institute of University Hospitals of Cleveland. “It
also illustrates the strength of combining research efforts at the hospital,
the university and industry. This kind of three-way collaboration is
essential for transferring our discoveries to the public.”
University Hospitals is the lead center for this study, and will enroll 12
patients with CF. The second site, Children’s Hospital of Denver in Colorado,
will send a team to Cleveland later in the spring to observe the procedures
before they begin enrollment.
This DNA compaction technology was developed at Copernicus Therapeutics and
is based on initial discoveries in the laboratory of Pamela B. Davis, MD,
Ph.D., Director of the Willard A. Bernbaum Cystic Fibrosis Research Center
and professor of pediatrics at Rainbow Babies & Children’s Hospital and CWRU,
and by Jose C. Perales, Ph.D., a former graduate student in the laboratory
of Richard W. Hanson, Ph.D., professor of biochemistry at CWRU. Dr. Davis,
Hanson and Perales are inventors of numerous patents assigned to CWRU School
of Medicine. The study is funded in part by The Cystic FibrosisFoundation.
New Method Used To Transfer Genes Into Mouse
4/2/2002
http://genomics.biocompare.com/gnews.asp?id=4420
Source: University of Minnesota
For the first time, a special segment of DNA called a transposon and an
enzyme known as the Sleeping Beauty transposase have been used to genetically
modify a vertebrate animal. In the study, which is published in the April
2 issue of the Proceedings of the National Academy of Sciences, University of
Minnesota researchers injected a transposon containing the gene for a yellow
coat color into a mouse embryo, resulting in a genetically modified mouse.
"This is a new type of technology, an entirely different way to make
genetically modified animals," said David Largaespada, Ph.D., an assistant
professor in the university's department of genetics, cell biology and
development and director of the University of Minnesota Cancer Center's
Genetic Mechanisms of Cancer research program. "The Sleeping Beauty
transposase enzyme plus the transposon is like a truck used to carry the
cargo, or specific genes, into the animal. These specific genes could help
treat diseases such as cancer."
Researchers at the Cancer Center injected a one-cell mouse embryo--a
fertilized egg--with a linear piece of DNA containing the transposon, along
with a source of Sleeping Beauty transposase enzyme. In this case, the
transposon contained the gene for making a yellow-colored coat. The enzyme
then caused the transposon to "jump" from the linear piece of DNA to a mouse
chromosome, where it was able to express its function of coat color.
"We're very excited about Sleeping Beauty’s potential," said Largaespada.
"One use would be to add genes to germ cells or early embryos in order to
produce large amounts of a protein in an animal. The protein then would be
purified and used as a drug treatment for hemophilia, for instance."
Another function would be to create genetically altered farm animals, which
could be used as a source of organs for transplantation. Gene identification
and function may also be determined by transposons' ability to mutate or
"knock out" genes.
"We and other scientists at the university, such as Scott McIvor, are also
working on transferring genes directly into cells of the body, in the liver
or lungs, for instance," said Largaespada. "We hope this procedure could help
cure diseases such as cystic fibrosis or hemophilia."
Largaespada is co-founder of Minneapolis-based Discovery Genomics, Inc.,
which has exclusive license to Sleeping Beauty and plans to commercialize
this technology. http://www.discoverygenomics.net/