快猫短视频

Pass it on

Mice really can inherit an artificial chromosome

IT TOOK more than a decade for the Human Genome Project to sequence the 24
different human chromosomes, but already other researchers are preparing to take
another huge step. They have shown it is possible make artificial chromosomes
that can pass from one generation to the next.

Such techniques might soon make it possible to treat patients by loading
their cells with extra chromosomes that are purpose-built to produce a
therapeutic protein and operate entirely independently of our natural
chromosomes. It might even be possible to treat genetic diseases with extra
chromosomes that can themselves be inherited, though this would mean challenging
the taboo against 鈥済ermline鈥 gene therapy.

The ground has been laid in experiments on animals at a Canadian
biotechnology company. A new paper by Deborah Co and her colleagues at Chromos
Molecular Systems in Burnaby, British Columbia, describes for the first time a
mouse that passed such a chromosome through three generations of descendants,
apparently without any harm to the animals.

Co鈥檚 experiments show that each generation of mice carried the new
chromosome, and that it was active. It served as a carrier for the gene that
makes beta galactosidase, a marker protein that turns blue on exposure to a
chemical.

The researchers started with a natural chromosome gutted of all its
functional genes but retaining other key elements
(快猫短视频, 23 October 1999, p 4).
These include the telomeres at the tips of chromosomes,
which protect them from fraying and recombining; the central, X-shaped
centromere, which orchestrates duplication during cell division; and regions of
satellite DNA at the root of each of the chromosome鈥檚 four arms, made up of
鈥渏unk鈥 genetic material bereft of working genes.

Co and her colleagues at Chromos have developed a way to implant genes into
the satellite DNA. They can implant multiple copies of the same gene, and
implant genes far larger than is possible in any other 鈥済ene shuttle鈥 technique
for ferrying DNA into cells. Once modified, the artificial chromosome can be
duplicated hundreds of thousands of times. The company says that the amount of
protein produced rises in step with the number of gene copies, and that the
chromosome does not interfere with natural chromosomes and so should be safer
than inserting genes into host DNA.

Because the company is about to sell shares on the Canadian stock market, it
is barred from talking to the media. But in a prospectus available to the
public, Chromos says it plans to insert the chromosomes into cells which will be
grown in fermenters to produce beneficial proteins and to genetically engineer
animals so that they produce valuable proteins in their milk. It has already
produced a second line of mice, this time carrying a gene that makes a
therapeutic antibody.

In a project with the Academic Medical Center at the University of Amsterdam,
Chromos is testing artificial chromosomes which produces a protein to ease the
symptoms of rheumatoid arthritis. The team inserts the chromosome into the
cultured cells of a rat with arthritis and then injects them into the rat鈥檚
joints. If the system works in rats, then trials could begin in people.

  • Source:
    Chromosome Research (vol 8, p 183)
  • More at: www.sedar.com/dynamic_pages/assoc_docs_e/d00014096.htm

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