Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Ancient DNA helps UF researchers unearth potential hemophilia therapy


A cut can be life-threatening for people with hemophilia, whose bodies don’t produce enough of a protein that prevents prolonged bleeding.

Now University of Florida researchers may be one step closer to finding a safe way to spur production of this missing protein in patients with the most common form of the hereditary bleeding disorder. Using a dormant strand of DNA that has quietly existed in fish for millions of years, the researchers replaced the faulty gene responsible for the disease in neonatal mice, according to findings published online this month in the journal Molecular Therapy.

"The degree to which these patients have problems from hemophilia stems from how much of this protein, factor VIII, is missing," said Bradley Fletcher, M.D., Ph.D., a UF assistant professor of pharmacology and one of the lead authors of the study. "If they have very low levels of it, they have lifelong problems of bleeding, but what’s even more problematic for them is they bleed into their joints, knees, hips and ankles, which limits their mobility."

Although hemophiliac mice don’t develop some of these more extreme symptoms of the disease, gene therapy prevented profuse bleeding in the animals, the findings show.

More than 18,000 Americans, nearly all men, have hemophilia A, the most common form of the disease, according to the Centers for Disease Control and Prevention. Currently, the only safe treatment for the disorder is a purified form of the protein, but it can cost patients thousands of dollars and its effects don’t last long. Scientists have been trying to find a safe way to perform gene therapy in hemophilia patients for years, but problems with the viruses typically used to transport needed genes to their target destinations have stymied their success, Fletcher said.

Researchers usually hide corrective genes inside viruses, which then infect cells. Without the virus to act as a key, the gene would be unable to enter the cell. But viral gene therapy has been associated with medical complications, and a few human patients have died as a result.

Instead, UF researchers used a novel nonviral approach, employing a strand of DNA present in modern-day fish called a transposon to transport the gene directly into the DNA of the mice. Nonviral therapy is thought to be safer, Fletcher said.

Transposons have the natural ability to bounce to different positions in DNA, allowing them to chauffeur genes into the cell. The transposon UF researchers used is one of a few that work in mammals, but until University of Minnesota scientists discovered it in 1997, it had remained hidden in the DNA of fish like trout for 15 million years. Years of mutations in the genetic code had buried the transposon, silencing its ability to issue molecular marching orders.

Fletcher and researchers Li Liu, M.D., Ph.D., an adjunct postdoctoral associate in the department of pharmacology and therapeutics, and Cathryn Mah, a UF assistant professor of pediatric cellular and molecular therapy, used the transposon to inject the gene into endothelial cells, which line blood vessels and other parts of the body. This was unique, Fletcher said, because the liver is generally considered the body’s powerhouse for producing the protein needed to keep hemophilia at bay. The study showed that these endothelial cells also can produce enough protein to correct the problem, he said.

"I think endothelial cells are potentially a very important cell to make factor VIII," said Katherine P. Ponder, M.D., an associate professor of medicine and a hemophilia researcher at Washington University in St. Louis. "They’re a very attractive cell type to express it."

It also was the first time researchers attempted such an approach on an animal so young. In adult mice, the immune system normally views clotting protein as an invader and rejects it after traditional gene therapy. But UF researchers bypassed this immune response by performing gene therapy on mice within 24 hours of their birth, when their immune systems were still naive and would accept the protein.

This type of approach cannot be used in human babies yet because doctors have no way of gauging how severe hemophilia is in newborns. Patients with mild disease will have fewer problems and the benefits of gene therapy may not outweigh risks to the baby, Fletcher said.

Ponder said she thinks the technique also may prove to share some of the same problems as viral-based gene therapy, potentially activating cells that cause cancer.

Now UF researchers are studying different ways to use the transposon and trying to find a way to overcome the immune attack when performing gene therapy on adult animals.

"I don’t think the research is done," Mah said. "But this is definitely a step forward for hemophilia gene therapy."

April Frawley Birdwell | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute

nachricht 'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

More VideoLinks >>>