Electroportation DNA -Non Viral Way

From: Spudboy100@aol.com
Date: Fri Jun 06 2003 - 13:52:58 MDT

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    http://www.wired.com/news/medtech/0,1286,59133,00.html

    Getting a gene inside cells to cure disease is the essence of gene therapy.
    It's also the biggest obstacle to making gene therapy work.

    Cells do what they can to prevent foreign objects from entering, so
    researchers have tried various methods to trick the cell into allowing access. None so
    far have been successful, and several gene therapy trials have been halted for
    safety reasons.

    Researchers studying a technology called electroporation, which uses pulses
    of electric current to prompt cells to become porous, believe their method
    might be a safer option.

    "People have tried gene therapy with retroviral or adenoviruses, and you have
    manufacturing issues, safety issues," said Robert Goodenow, vice president of
    business development at Gentronics in San Diego, California. "We feel that
    using a physical method like electroporation can end up being cheap and safe."

    Viruses are good at getting inside cells, so researchers have tried to
    piggyback genes on them while altering the virus to remove its harmful qualities.
    But that method resulted in the death of 18-year-old Jesse Gelsinger in 1999,
    and researchers as well as patients have been wary of the viral method ever
    since.

    Electroporation, on the other hand, doesn't require a viral vector, since it
    uses a transient electric current to open up the cell wall. Researchers at
    Genetronics have made progress recently using this method to deliver an HIV
    vaccine, as well as to grow new blood vessels in animals.

    Their work with HIV is a collaboration with Chiron, the biotech company that
    provided the DNA, and is closest to being tested in humans. Now, they're
    testing the technology in primates, where they've seen encouraging results.

    The gene-therapy vaccine introduces a bit of HIV DNA into cells using
    electroporation. In primates, the treatment has induced a strong immune response that
    makes the researchers hopeful it will also work in humans.

    Humans have two kinds of immunity: antibodies that attack specific foreign
    entities in the body, and T-cells, a type of white blood cell that kills
    infected cells. T-cells are most important in the fight against HIV -- antibodies
    alone can't kill the virus.

    "If you're an HIV patient and you have generated a strong antibody response,
    that's not going to help you unless you can develop a strong T-cell response
    also," Goodenow said. "We enhanced the production of not only antibodies but
    also T-cells."

    Genetronics is also using electroporation along with a balloon catheter --
    similar to the type used in an angiogram -- to deliver DNA that encourages the
    growth of blood vessels.

    Cardiovascular disease can cause the death of peripheral blood vessels, which
    can lead to ulcers, infection and even amputation.

    To avoid this, Genetronics, in collaboration with Boheringer Ingleheim has
    developed a catheter connected to a balloon that contains DNA, which is fed into
    the artery.

    "The trick was we coupled that to electroporation," Goodenow said.

    In mice, the electroporation opened up muscle cells to deliver the growth
    factor, which led to new arteries.

    The catheter platform could be used to deliver everything from gene therapy
    to topical anesthetics to collagen as an anti-aging treatment, Goodenow said.

    Some researchers are using different means to get gene therapy into cells.
    Jonathan Vogel, an investigator in the dermatology branch at the NCI takes skin
    from a mouse, and subjects it to gene therapy using a viral vector in a dish.

    He then grafts the skin back onto the mouse. The goal is to get the gene into
    the bloodstream so it will have a therapeutic effect throughout the body. For
    example, it could generate a clotting factor for hemophiliacs, or insulin for
    diabetics.

    "The cells are used as factories," Vogel said.

    Genetronics is collaborating with Genteric to develop a similar systemic
    method by injecting genes into salivary glands, then electroporating the area so
    cells will absorb them and carry them through the bloodstream.



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