- A chip that will automatically create
hundreds of cloned embryos at a time is being developed by a Californian
biotech company, New Scientist has learned.
If it lives up to its promise, the chip should help make cloning cheap
and easy enough for companies to mass-produce identical copies of the best
milk or meat producing animals for farmers. It might even be used for cloning
human embryos.
The chip automates the laborious process of nuclear transfer, the key step
in cloning. At present it takes hours of painstaking work with a microscope
to remove the nucleus of an egg cell and replace it by fusing the denucleated
egg with another cell.
"If somebody's got something like that, obviously it would make everybody's
life easier," says Tanja Dominko of Advanced Cell Technology, the
Massachusetts company that caused a stir late last year when it announced
that it had created cloned human embryos.
- Urchin eggs
- In animals, cloning is still very wasteful.
At best, around half of cloned embryos develop to the point where they
can be implanted, and only a tenth of these survive to birth. Often more
than a hundred nuclear transfers must be carried out to create a single
clone.
Scientists usually start with a batch of 150 eggs, and denucleate them
one at a time before moving on to the next step. That means eggs can be
left sitting around for several hours, a delay that may reduce success
rates.
But the nuclear transfer array developed at Aegen Biosciences, by the company's
founders Richard Kuo and Gregory Baxter, could handle hundreds or even
thousands of eggs at once. Kuo says they can routinely denucleate 30 to
50 sea urchin eggs at a time. They plan to start testing cow eggs in the
next few weeks.
The prototype is a thin silicon slice a few centimetres across etched with
hundreds of tiny wells, one for each egg. The trick is to spin the chip
in a centrifuge, forcing the eggs' dense nuclei through a small hole at
the bottom of each well. About 90 per cent of the eggs can be successfully
denucleated this way, Kuo says.
Kuo and Baxter are now working on the next step, which is to fuse a donor
cell with the denucleated egg. A lid with appropriately positioned donor
cells will be placed on top of the eggs. "Then they're ready to fuse,"
says Kuo, although he won't reveal details of the method. After fusion,
eggs that develop far enough could be implanted manually into an animal's
womb as normal.
- Too expensive
- "If it works with cow [eggs], that
would be very neat," says Rudolph Jaenisch of MIT, who studies problems
with cloning. But just because it works with sea urchins doesn't guarantee
that it will work with the eggs of other species, he warns.
And Randall Prather of the University of Missouri, whose team recently
announced the cloning of miniature pigs, says the chip won't help solve
other problems, such as ensuring that the eggs you use have been kept in
the right conditions. He thinks it might also be too expensive for many
labs.
Kuo admits there is much work still to be done on the chip, but he believes
it's worth the effort. One could submit different batches of eggs to various
treatments, to find out which conditions improve success rates in cloning,
he says. Such studies could also help researchers identify the factors
in eggs that reprogram the added nucleus.
If the chip does improve success rates in animals, it is likely to be used
to create cloned human embryos, where the problem is not dealing with many
eggs at a time but getting hold of sufficient numbers of eggs. Companies
such as Advanced Cell Technology hope to obtain embryonic stem cells from
cloned embryos but have had only limited success.
The chips might also appeal to the mavericks who want to carry out human
reproductive cloning despite all the warnings about the risks. The warnings
are based on the health problems seen in the few clones that do survive,
which have also prompted the FDA to ask companies not to sell food from
clones until it has been proved to be safe.
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- http://www.newscientist.com/news/news.jsp?id=ns99991863
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