---------- Forwarded message ----------
From: Hughes, James J. <james.hug...@trincoll.edu>
Date: Thu, Jan 22, 2009 at 7:53 PM
Subject: [tt] A Virus That Rebuilds Damaged Nerves
To: t...@postbiota.org


http://www.technologyreview.com/printer_friendly_article.aspx?id=21991

Thursday, January 22, 2009

A Virus That Rebuilds Damaged Nerves
Genetically engineered viruses could form a scaffold for nerve cells.

By Katherine Bourzac

Viruses that mimic supportive nerve tissue may someday help regenerate
injured spinal cords. While other tissue-engineering materials must be
synthesized and shaped in the lab, genetically engineered viruses have
the advantage of being self-replicating and self-assembling. They can be
designed to express cell-friendly proteins on their surfaces and, with a
little coaxing, be made into complex tissuelike structures. Preliminary
studies show that scaffolds made using a type of virus called a
bacteriophage (or phage) that infects bacteria but cannot invade animal
cells can support the growth and organization of nerve cells.

Researchers working on tissue engineering hope to eventually be able to
use a patient's own cells to grow replacement tissue for damaged hearts,
livers, and nerves. But mimicking the structure and function of the
body's tissue has proved difficult. Matrices of supportive, fibrous
proteins sustain the cells of the heart, lungs, and other tissues in the
body. These scaffolds provide both structural support and chemical
signals that enable an organ or nerve tissue to function properly.

Some biological engineers are using scaffolds made of polymers to try to
mimic the supportive matrix of real tissue. Seung-Wuk Lee, a bioengineer
at the University of California, Berkeley, has turned to viruses
instead. "Viruses are smart materials," he says. "Once you construct the
genome, you can make billions of phages, and they're self-replicating
materials." The phage that Lee is working with, called M13, is long and
thin like the protein fibers that make up the cellular matrices inside
the body.

First, Lee and his colleague Anna Merzlyak genetically engineered M13 to
display nerve-friendly proteins on their outer coats. These proteins are
known to help nerve cells proliferate, adhere, and extend into long
fiberlike shapes. Next, the researchers grew large numbers of the
viruses in bacterial-cell hosts and dropped them into a solution
containing neural-progenitor cells. These cells are more fully developed
than stem cells but are still young and need coaxing to form new
tissues. In the solution, the viruses align themselves like a liquid
crystal, says Lee. He and Merzlyak used pipettes to inject the solution
into agar, a Jell-O-like cell-culture medium, creating long, nerve-like
fibers of the virus interspersed with cells. The progenitor cells then
multiplied and grew the long branches characteristic of neurons. Lee
says that the phage are well suited to making long, fiberlike structures
such as nerve tissue but can also be made into more complex structures
by varying their concentration or manipulating their position with a
magnetic field.

Lee is not the first to use a virus as an engineering material. Other
researchers have used the same virus to build battery electrodes. Using
the virus in this way was pioneered by Angela Belcher, now a professor
of materials science and engineering and of biological engineering at
MIT, and was the basis of Lee's graduate work while he was in her lab.
Genetically engineered phages have already been approved as an
antibacterial food preservative by the U.S. Food and Drug
Administration, for use in lunch meats like bologna, for example. Phages
are also under study as a potential treatment for chronic bacterial
infections.

MIT Institute Professor Robert Langer says that Lee's work is
interesting from a materials perspective, but he cautions that its
practicality must be established through in vivo studies.

Lee says that his group plans to establish the safety of phage scaffolds
in live animals next. M13 has a good safety record and is not capable of
infecting people. Still, the Berkeley researchers will need to
investigate how an animal's immune system responds to the viral
scaffolds and prove that they encourage nerve regeneration once inside
the body. Lee hopes that the viral system will eventually be used to
regenerate neurons in patients with spinal-cord injuries.

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